AU626806B2

AU626806B2 - Novel amide derivatives, processes for production thereof, and agricultural-horticultural fungicide containing them

Info

Publication number: AU626806B2
Application number: AU24147/88A
Authority: AU
Inventors: Tsutomu Ishii; Yoshiro Kanemoto; Toshiaki Kuwatsuka; Shuji Ozawa; Takeshi Sekino; Hitoshi Shimotori; Keiko Shinada; Yoshinori Tanaka; Hideo Yamazaki; Yuji Yanase
Original assignee: Mitsui Toatsu Chemicals Inc
Current assignee: Mitsui Toatsu Chemicals Inc
Priority date: 1987-10-23
Filing date: 1988-10-21
Publication date: 1992-08-13
Anticipated expiration: 2008-10-21
Also published as: DE3883695T2; AU2414788A; BR8805475A; HUT49595A; KR900006746B1; US5104886A; KR890006638A; ES2058209T3; CN1066363A; US4980363A; DE3883695D1; EP0313091A2; HU203881B; EP0313091A3; EP0313091B1

Description

AUSTRALIA

Patents Act COMPLEYf SPECIFICATIK

(ORIGINAL)

Class Int. Class Application Number: Lodged: Complete Specification Lodged: Accepted; Published:

IPA

6 2 0 Priority Related Art: APPLICAT'S iiPFERFicE: K- 102 (Toatsu/17 Name(s) of hpplicant(s): Mit-sui Toatsu Chemicals, Inc 0 o4 0 go Address(es) of Applicant(s): 2-5, Kasuinigaseki 3-choncf, Chiyoda-ku,, Tokyo,

JAPAN.

Address for Service is: PHILLIPS ORKt =DE FITZPATrRICK Patent and Traele Hark Attorneys 367 Collins Street Ihelbourne 3000 AUSTRALIA SComplete Specification for the invention entitled: YWEL Am1I)p. DERIVATIVE, PiXXCESSES FOR PIJUCTICKl "11MEOF, AMD 1micuU RAL-HORTICUL URAL FUNGICIDE CONiTAINING THEM 0 Wo 9 Q9999~ 9 9 94 9 9 96 4 99 Our Ref 111004 POF Code: 1349/1719 The following statenient is a full description of this invention, includi the best method of performing it k.nown to applicant(s): ngL 6003q/1 1 1 1 1.

1 A- This invention relates to an amide derivative represented by the following general formula (I)

R

1

R

2 R X R Y r CONHCH f

(I)

0 0, wherein one of X and Y represents a sulfur atom and the other represents a carbon atom, Z represents a nitrile or thioamide group, each of R 1 and R 2 represents a hydrogen atom, a halogen atom, an alkyl group having 1 to 6 carbon atoms, a halomethyl group or a phenyl group, and R 3 represents an alkenyl group having 2 to 6 carbon atoms, a haloalkenyl group having 2 to 4 carbon atoms, a furyl group, a thienyl group, an alkoxy group having 1 to 4 carbon atoms, an alkylthio group having 1 to 4 carbon atoms, an alkynyloxy group having 3 to carbon atoms, an alkynylthio group having 3 to carbon atoms, a pyrazolyl group, or an unsubstituted or halo-substituted phenyl group; processes for producing the amide derivative; an agricultural-horticultural fungicide comprising the amide derivative as an active ingredient; and to an agricultural-horticultural fungicidal composition comprising the amide derivative of general formula as a first active ingredient and at least one member selected from 25 the group consisting of acylalanine fungicides having the action of corntrolling plant diseases caused by Oomycetes, dithiocarbamate fungicides, N-halcalkylthioimide fungicides, inorganic copper fungicides, tetrachloroisophthalonitrile, dichlofluanide and fluazinam.

0 0n 0 0c 0 0) 0 0 0v~o r

I

2 Heretofore, compounds having various chemical structures have been used as agricultural-horticultural fungicides, and greatly contributed to the control of plant diseases and consequently to the development of agriculture. But these conventional fungicidal chemicals have not proved to have sufficient controlling activity and safety. For example, some of dithiocarbamate fungicides such as zinc ethylenebis(dithiocarbamate) [zineb], manganese ethylenebis(dithiocarbamate) [maneb], a complex of manganese ethylenebis(dithiocarbamate) and zinc ethylenebis(dithiocarbamate [mancozeb] and dizinc bis- (dimethyldithiocarbamate) ethylenebis(dithiocarbamate) [polycarbamate], N-haloalkyl thioimide fungicides such as N-trichloromethylthio-4-cyclohexene-l,2-dicarboximide [captan], ,2',2'-tetrachloroethylthio-4-cyclohexene-1,2-dicarboximide (captafoll and N-trichloromethylthiophthalimide [folpet], inorganic copper fungicides such as cupric sulfate, basic cupric sulfate, basic cupric chloride and cupric hydroxide, tetrachloroisophthalonitrile [TPN], N-(dichlorofluoromethyl- 0? thio)-N' ,N-dimethyl-N-phenylsulfamide[dichlofluanide] and 3-chloro-N-(3-chloro-5-trifluoromethyl-2-pyridyl)-2,6dinitro-4-trifluoromethylaniline (fluazinam] show an ooutstanding control efficacy on diseases of plants such as fruit trees and vegetables and are widely used as 1 agricultural-horticultural fungicides. However, these chemicals mainly exhibit a preventive effect and are not expected to produce a curative effect. Hence, they have the serious defect that when a plant disease is seen to occur, these chemicals are not expected to give a *o «sufficient efficacy. When chemical application for controlling plant diseases is considered in an actual situation, the chemicals are more or less sprayed after ,the occurrence of plant disease symptons, and the abovecited chemicals are difficult of controlling the diseases completely. Furthermore, the concentrations of these chemicals at which they exhibit a control effect are very 1 [Id r n-

I_

j 1-

I:

i;- 3 high so that they are difficult to use safely, and some of these chemicals have an unnegligible toxicity to fish, In order to eliminate these defects, extensive research work has been done on new controlling agents.

For example, acylalanine fungicides, such as N-(2,6dimethylphenyi)-N-(2'-methoxyacetyl)alanine methyl ester talaxyl N-(2,6-dimethylphenyl) -N-(2-furoyl)alanine methyl ester [furalaxyll, N-(2,6-dimethylphenyl)-N- (phenylacetyl)alanine methyl ester [benalaxyl], (2-chloro- N-(2,6-dimethylphenyl)-N-(tetrahydro-2-oxo-3-furanyl)acetamide [ofuracel and 2-methoxy-N-(2,6-dimethylphenyl)- N-(2-oxo-l,3-oxazolidin-3-yl)acetamide [oxadixyl] were developed as controlling agents on plant diseases caused by Oomycetes which also have an excellent curative effect 1 have been developed and come into practical use worldwide. It has already been pointed out that resistant strain to these chemicals have appeared and their control effect have consequently decreased.

Many active benzylamide compounds have been discovered and used as herbicides or fungicides. For example, known substituted benzamide derivatives include ethyl N-benzoyl-N-(3,4-dichlorophenyl)-2-aminopropionate [benzoylprop ethyl] as herbicide, and N-(3-isopropoxyphenyl)-2-methylbenzamide [mepronill as fungicide.

BP-2094786, BP-2095237, and BP-2107308 disclose a herbicide and a fungicide comprising a substituted benzylamide derivative having a 4-pyridylcarbonyl, 2furylcarbonyl, 2-thienylcarbonyl or 2-benzofurylcarbonyl group, but its phytotoxicity on crop plants is a problem.

30 It is an object of this invention to provide a compound being free fiom the above-mentioned defects of the prior art and having excellent properties as an agricultural-horticultural fungicide; processes for production thereof, and an agricultural-horticultural fungicide comprising the compound as an active ingredient, and an agricultural-horticultural fungicidal Sa a) a a a aa a oa d 4 composition comprising the compound as a first active ingredient and a specific known fungicidal compound as a second active ingredient. More specifically, the invention provides a compound which has a preventive and a curative effect on a wide range of plant diseases such as diseases of fruit trees and vegetables, shows an excellent control effect against resistant fungi, has a wide range of applicability and a long residual effect, does not show phytotoxicity on crop plants, and possesses very low toxicity on warm-blooded animals and fish; simple processes for production thereof in high yields; an agricultural-horticultural fungicide comprising the compound as an active ingredient; and an agriculturalhorticultural fungicidal composition comprising the compound as a first ingredient and a specific known fungicidal compound as a second active ingredient.

We worked extensively on acylamide derivatives in order to achieve the above object, and have found that amide derivatives having a thiazole or isothiazole ring have biological activity which cannot at all be an- So ticipated from the above-exemplified compounds and an excellent controlling effect on a wide range of plant diseases; and that particularly, these amide derivatives have both a preventive and a curative effect in controlling various crop diseases such as late blight and downy mildew.

Thus, according to this invention, there is S, first provided an amide derivative represented by the following general formula (I) 1 2 30 R 1

R

0X Yah YONHCH 3 ,Y

(I)

0 a 0 S wherein one of X and Y represents a sulfur atom and the other represents a carbon atom, Z represents a nitrile or thioarnide group, each of R 1and R2 represents a hydrogen atom, a halogen atom, an alkyl group having 1 to 6 cairbon atoms, a halomethyl giu or a phenyl group, and R 3 represents an alkenyl group p aving 2 to 6 carbon atoms, a haloalkenyl group having 2 to 4 carbon atoms, or an unsubstituted or halo-sub 'tituted phenyl group.

In the amide derivat ye of general formula examples of the alkyl group frRTadR2are methyl, ethyl, n-propyl, iso-propyl, n-butyl, i-butyl, sec-butyl, tert-butyl, n-pentyl and n-hexyl groups. Examples of the halomethyl group are chloromethyl and tr-*fluoromethyl groups.

The alkenyl group for R 3is, for example, a vinyl, allyl, propen-1-yl, 2-methylpropen-1-yl, l-methyl-propen-l-yl, 1, 2-dimethylpropen-l-yl, 2-ethylpropen-l--yl 0r 2-npropylpropen-l-yl group. The haloalkenyl group i's, for example, a 2-chloroethenyl, 2-chloropropen-1-yl, or 1-methyl-2-chloropropen-1-y. group. Examples of the alkoxy group are methoxy, ethoxy, r)-propoxy, iso-propoxy, n-butoxy, sec--butoxy and tert-butoxy gjroups., The halogen atom may be ,2(71 for exampl~e, fluorine, chlorine, bromine or iodine.

LL

-6- Compounds represented by the following general formula (IV) 1 2 Y ONHCH (IV) N

R

wherein one of X and Y represents a sulfur atom and the other represents a carbon atom, each of R 1 and

R

2 represents a hydrogen atom, a halogen atom, an alkyl group having 1 to 6 carbon atoms, a halomethyl group or a phenyl group, and R 3 represents an alkcnyl group having 2 to 6 carbon atoms, a haloalkenyl group having 2 to 4 carbon atoms, a furyl S. group, a thienyl group, an alkoxy group having 1 to 4 o* carbon atoms, an alkylth. group having 1 to 4 carbon atoms, an alkynyloxy group having 3 to 5 carbon atoms, an alkynyloxy group having 3 to 5 carbon o r atoms, an alkynylthio group having 3 to 5 carbon atoms, a pyrazoly1 group or an unsubstituted or halogen-substituted phenyl group, may be prepared by a process which comprises reacting a heterocyclic 5-membered carboxylic acid represented by the following general formula (II) 1 2 R R SY O2 (II)

N

wherein X, Y, R and R are as defined above, or its rsective derivative wi.tn an aminoacetonitrile represented by the following general formula (III)

CN

H N-C

I)

2 -R 3

I

wherein 3 is as defined above, W dy

I

7or its salt; a process for producing an amide derivative represented by the following general formula (IV)

R

1

R

2 A ONHCH (IV)

N

wherein one of X and Y represents a sulfur atom and the other represents a carbon atom, each of R and R 2 represents a hydrogen atom, a halogen atom, an alkyl group having 1 to 6 carbon atoms, a halomethyl group or a phenyl group, and R represents an alkoxy group having 1 to 4 carbon atoms, an alkylthio group having 1 to 4 carbon atoms, an alkynyloxy group having 3 to carbon atoms, an alkynylthio group having 3 to carbon atoms, or a pyrazolyl group, which comprises halogenating an N-cyanomethvlcarboxylic acid amide represented by the following general formula

(V)

1 2 R I Y '-CONHC'a2CN (V) o (2 wherein X, Y, R and R 2 are as defined above, to form an intermediate represented by the following general formula (VI) R

R

2 Y CONHCH-CN

(VI)

N Hal 0 4 wherein X, Y, R 1 and R are as defined above, and Hal represents a halogen atom, /i 8 and then reacting the compound of general formula (VI) with a compound represented by the following general formula (VII.)

HR

3

(VII)

wherein R 3 is as defined above; and a process for producing a compound represented by the following general formula (VIII)

R

1 R 2

X

I _-N^cHCSNH2 SONHCH 3

(VIII)

N

wherein X and Y represent a sulfur or carbon atom, each of R 1 and R 2 represents a hydrogen atom, a halogen atom, an alkyl group having 1 to 6 carbon atoms, a halomethyl group or a phenyl group, and R 3 represents an alkenyl group having 2 to 6 carbon atoms, a haloalkenyl S 15 group having 2 to 4 carbon atoms, a furyl group, a thienyl group, an alkoxy group having 1 to 4 carbon atoms, an alkylthio group having 1 to 4 carbon atoms, an alkynyloxy group having 3 to 5 carbon atoms, an alkynylthio group having 3 to 5 carbon atoms, a pyrazolyl group or an unsubstituted or halogen-substituted phenyl group, o which comprises subjecting a compound represented by the following general formula (IV)

R

1

R

ox Y I-CONHCH (IV) \N R It 0 wherein X, Y, R and R 3 are as defined above, S7

I

9 to addition-reaction with hydrogen sulfide.

The processes for producing the amide derivatives of the invention are sh-Ywn by the following reaction schemes to Reaction scheme (a) 1 2

CN

I 0 2 H 2 NCHR 3

N

(II) or its reactive (III) derivatives 1 2 R R

CN

ONHCH

N

(IV)

In this scheme, the amide derivative of general formula (IV) can be produced by reacting the heterocyclic carboxylic acid of general formula (II) or its reactive derivative (such as an acid chloride or an acid anhydride) with the aminoacetonitrile of general formula (III) or its salt. Various methods are available in performing the reaction in scheme and will be described below with reference to the following reaction schemes to Reaction scheme (a)-l Method comprising converting the carboxylic acid into a chloride and reacting it with the aminoacetonitrile:- 6 4 10 1 2 1 2 R R R R 2H SOC 2 Y -OC1 N N

(II)

-CN

H NR 2 \R 3 R1 R2 (III) N CN ONHCH 3 N

(IV)

Usually, the carboxylic acid derivative (II) is heated in an excess of thionyl chloride. After the reaction, the excess of thionyl chloride is evaporated to obtain the acid chloride. Sometimes, the reaction does not proceed well in thionyl chloride. In such a case, the carboxylic acid (11) is treated with a nearly equivalent weight of phosphorus pentachloride in an inert solvent. This makes the reaction proceed smoothly.

After the reaction, low-boiling materials are evaporated to give the acid chloride. The resulting acid chloride is reacted in an inert solvent with the aminoacetonitrile (III) or its salt in the presence of an equivalent weight, or a slightly excessive amount, of a base to give the amide derivative (IV) easily. When the salt of the aminoacetonitile is used, the base is additionally supplied in an amount required to neutralize the salt.

o o The inert solvent is inert to the chloride and the aminoacetonitrile. Specific examples are ethers such as eo° diethyl ether, diisopropyl ether, tetrahydrofuran and ao o dioxane, hydrocarbons such as benzene, toluene, xylene and ligroin, halogenated hydrocarbons such as dichlocomethane, chloroform and carbon tetrachloride, esters such o0o0 25 as ethyl acetate and ethyl propionate, and aprotic polar solvents such as NN-dimethylformamide, dimethyl sulfoxide and 1,3-dimethylimidazolidinone. Pyridine may be itr i F I i r- 11 used as the base and the solvent. Examples of base may be organic bases such as triethylamine, dime6rylaniline, pyridine and DBU, and inorganic bases such as ammonia, potassium hydrogen carbonate, potassium carbonate, siodium carbonate, sodium hydrogen carbonate, sodium hydroxide and ammonium carbonate, although these examples are not limitative. It is not desirable to perform this reaction at too high temperatures because the thermal stability of the intermediate aminoacetonitrile derivative (III) is low.

Preferred reaction temperatures are 10 to 50 oC. After the dropwise addition of the aminoacetonitrile derivative (III), the mixture is continuously stirred at room temperature in order to complete the reaction. The reaction time, which varies depending upon the reaction temperature, is usually 0.5 to 4 hours. After the .eaction, the crude reaction product is obtained by a customary method.

The resulting desired amide derivative can be easily isolated and purified by a conventional method such as recrystallization or column chromatography.

Reaction scheme (a)-2 Method comprising reacting an anhdyride of the carboxylic with the aminoacetonitirle.

R

1 R2 R 1 2 R R R R J2 j .(It)

OCN

H NCN 3 1 2 4 2 R3

R

1

R

2 (111) CN Y_ )Jj ONHCH o 3 N

(TV)

oa s .44; j, A

-I

I

12 The amide derivative (IV) can be obtained by carrying out the same reaction as in reaction scheme except that the acid anhydride is used instead of the acid chloride.

Reaction scheme (a)-3 Method comprising reacting a mixed acid anhydride of the carboxylic acid with the aminoacetonitrile.

1 2 1 2 R X CC R 4 X 0 0 CO H Y -O-C-OR4 N N

(II)

CN

H NCH 3 1 2 2 NR 3

R

1

R

(III) CN Y ONHCH

(IV)

(In the above scheme, R 4 represents a lower alkyl group.) The carboxylic acid derivative (II) is dissolved in an organic solvent, and in the presence of a o 15 base, a chlocoformate ester is added to form a mixed acid anhydride. Addition of the aminoacetonitrile (III) to the mixed acid anhydride gives the amide derivative (1V).

The organic solvent and the base may be quite the same as those used in the teaction of scheme The reaction o 20 temperature is -50 to 0 C, preferably -10 to 10 0 C, for the reaction of the carboxylic acid with the chloroao formate, and 0 to 50 oC, preferably 10 to 30 for the reaction of the mixed anhydride with the aminuacetonitrile. The isolation and purification of the final S 5 product can be easily carried out in accQrdance with a conventional method as in the case of reaction scheme b t 13 Reaction scheme (a)-4 Method comprising using carbonyldiimidazole

(CDI).

1 2 R x R ^-CO2HO

N

(II)

O

N- N" N N-C-N _j(CDI)

N-

R

1

R

2 R R x -N Y j -O-C-N j

N-

H N CH- 2 R

R

1

R

2

CN

RR (INHCH

(IV)

ri~ I I o I The carboxylic acid derivative (II) is dissolved in an organic solvent, and carbonyldiimidazole is added. Then, at 0 to 50 0 C, preferably 0 to 30 the aminoacetonitrile (III) is added to give the amide derivative The organic solvent used may be the same as that used in the reaction of reaction scheme The isolation and purification of the final product can be easily carried out in a customary manner in the same way as described with regard to the reaction in reaction scheme Reaction scheme Method comprising using dicyclohexylcarbodiimide (DCC).

~1_I i It- a 14 14

R

1

R

2

O-N=C=N

0yI O2OH S (DCC) R -CO2 C N

CN

H N CH.- 2 R 3

R

1

R

2 (III) ONHCH

N

Y I N H C H N

(IV)

The carboxylic acid derivative (II) is dissolved in an organic solvent, and dicyclohexylcarbodiimide is added to the solution. While the solution is cooled with ice water, the aminoacetonitrile (III) is added to give the amide derivative. The organic solvent used in this reaction may be the same as those exemplified with regard to reaction scheme The isolation and purification of the final product can be carried out 4 teasily by a conventional method.

In addition to the reactions uown in reaction schemes to methods usually empoloyed in the field of peptide synthesis may be used for the production of the amide derivatives of the invention.

Where R 3 in general formula (IV) is an al!:oxyv alkylthio, alkynyloxy, alkynylthio or pyrazolyl group, the amide derivative (IV) can be produced by the follow- 20 ing process t I& c 0 t 15 Process (b) bromine 1 2 and ethyl 1 R 2 X acetate as X Y ONHCH 2 N so vent ONHCH CN N N Br

(VI)

1

R

2 3

CN

HR (VII) HR V I I

YONHCH

triethylamine R3

N

(IV)

An N-cyanomethylcarboxylic acid amide (V) corresponding to formula (IV) in which R 3 is a hydrogen atom is very important as a synthesis intermediate for a compound of general formula (IV) in which R 3 represents an alkyloxy, alkylthio, alkynyloxy, alkynylthio or pyrazolyl group.

Treatment of the N-cyanomethylcarboxylic acid amide with a halogenating agent in a suitable solvent gives a halogenated intermediate Bromine or N-bromosuccimide may be used as the halogenating agent. Examples of the solvent are aliphatic halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride and 1,4-dichloroethane, and aliphatic carboxylic acid esters such as methyl acetate, ethyl acetate, isopropyl acetate and ethyl propionate. The reaction temperature is 20 to 80 preferably 30 to 50 This reaction may be carried out in an atmosphere of an inert gas.

Since the halogenation intermediate (VI) is unstable, it is immediately reacted with HR (VII). This reaction is o a acarried out in the presence of an acid acceptor. Examples of the acid acceptor are tertiary amines such as triethylainine and dimethylaniline, although they are not limitative.

Desirably, this reaction is carried out in a solvent or diluent. It is desirable to avoid high temperatures in LV a

F

16 carrying out this reaction because the thermal stability of the intermediate is low. Desirabl:, it is carried out under cooling because it is exothermic. The desired amide derivative (IV) may be purified in a customary manner by recrystallization, column chromatography, etc.

A compound of formula (VIII) corresponding to a compound in which Z is a thioamide group may be carried out by the following process Process (c)

R

1

R

2

R

1

R

2 SON C HCN H S -CSNH 2 ONHCH R 3 N OHCHR 3 N N (IV) (VIII) The thioamide derivative (VIII) can be obtained by treating the compound (IV) with gaseous hydrogen sulfide in the presence of a catalytically effective amount of a tertiary amine in an inert solvent, for example aliphatic halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride and fal, 1,4-dichloroethane, or aliphatic carboxylic acid esters such as me t hyl acetate, ethyl acetate, isopropyl acetate and ethyl propionate. The isolation and purification of S 20 the desired product may be easily carried out in a customary manner by recrystallization, column chromatography, etc.

Methods of synthesizing the heterocyclic membered carboxylic acid iII) as the starting material 25 used in this invention are described below by citing references.

Thiazole-4-carboxylic acids (Journal of «o Chemical Society, 1946, page 87) i' I 17 S 0 R -C-NH 2 RrCH 2 C-C 2

C

2 H 5 ref luxed in benzene for 24 hrs.

KNa C0 2 C 2 H 5 <S NaOH N

CO

R

S~

Thiazole-5-carboxylic acids (Chemical Abstracts, vol. 40, page 4056) S 0 1 11 2_11___ C-NH 2 R -C-CH-C 2 C 2 H 5 Hal, Sl~1 CO 2

C

2 H5 NaOH R

N

S CO 2

H

This is the so-called Hantzsch reaction.

143) Isothiazolecarboxylic acids (journal of Chemical Societty, 1959, pa~ge 3061) *0 c' oo 0 000k 04 o 0 0 0~ 9 .0 0~0 9 0 9 0 09 0 0 09 4 9~ 04 0 44 0994 9 990044 4 9 904041 0 9 19 a 4 4 a. 40 Sandmeiyer ceaction N-Ns NH 2 n"S Br I

I

N J 02H CuCN

C

e%4) 2-Halogenothiazole--5-carboxylic acids (journal of Heterocyclic Chemistry, vol. 22, page 1621, 1985) 12 18 0 R-C-C H 2

CO

2

C

2

H

5

S

NH

2

-C-NH

2

O

SOC1 2 o

R

1

-C-CH

2

CO

2

C

2

H

Cl

N

SNH 2O2C2H CO 2

C

2

H

(HNO

2 CuCl or

(HNO

2 CuC 2) or (HNO Na 2 H2OH 2

R

1 Hal

CO

2

C

2

H

Hal CO2

H

"'^s2 The aminoacetonitrile (III) can be easily obtained by the so-called Strecker reaction shown below.

H CH NH 3 P-CHO HO-CH' 3 MCN R 3CN (IX)

H

2 N-CH'R 3

(III)

oft,, ftftftteft ftft ftg I, ft I ft ft ft ft.

ft ftftft4 ~ft ft ft ftftftft ft ft tJ ft ft ft.

ft ft~ (In the above scheme, Hal represents a halogen atom.) Specifically, it can be obtained easily by reacting an aldehyde of general formula (IX) with hydrogen cyanide M=H1 or an alkali metal cyanide M=alkali metal] and ammonia or ammonium chloride in water or in a two-layer system composed of water and an organic solvent. The sequence of adding the aldehyde the cyanide and ammonia or ammonium chloride is arbitrary. In any case, this reaction proceeds more efficiently in the presence of a phase transfer catalyst.

The resulting aminoacetonitrile is desirably submitted to the next step immediately because it is unstable. If, 19 however, it is converted to a mineral acid salt, it becomes a stable solid and can be stored for a long period of time.

The present invention further provides an agricultural-horticultural fungicide comprising a diluent or a carrier and/or an adjuvant, and as an active ingredient, an effective amount of at least one amide derivative represented by the following general formula

(I)

1 2 R R X

Z

ONHCH i N

R

wherein one of X and Y represents a sulfur atom and the other represents a carbon atom, Z represents a nitrile or thioamide group, each 1 2 of R and R represents a hydrogen atom, a halogen atom, an alkyl group having 1 to 6 carbon atoms, a halomethyl group or a phenyl group, and R 3 represents an alkenyl group having 2 to 6 carbon atoms, a haloalkenyl group having 2 to 4 carbon atoms, a furyl group, a thienyl group, an alkoxy group having 1 to 4 c6rbon atoms, an alkylthio group having 1 to 4 carbon atoms, an alkynyloxy group having 3 to carbon atoms, an ,lkynylthio group having 3 to 255 carbon atoms, a pyrazolyl group, or an uno 25 substituted or halo-substituted phenyl group.

When the compound of this invention is to be o 04 used as an agricultural-horticultural fingicide, it shows 0,0 0. an excellent control effect against a broad range of plant diseases. It is especially effective against late blight and downy mildew of various crops caused by Oomycetes. The main diseases to be controlled are potato i late blight (Phytophthora infestans), tomato late blight -CI i; i L;lil I~ i 20 (Phytophthora infestans), tobacco black shank (Phytophthora nicotiana var. nicotiana), strawberry red stele (Phytophthora stem and root rot of soybean (Phythophthora megasperma var. sojae), grape downy mildew (Plasmopara viticola), cucumber downy mildew (Pseudoperonospora cubensis), hop downy mildew (Pseudoperonospora humuii), spinach downy mildew (Peronospora spinaciae), and dampingoff or seedling blight of various crops caused by aphanomyces, Pythium, etc. Another great charactristic of the amide derivatives of the invention is that when applied to crops, they hardly show phytotoxicity which is seen with other amide derivatives.

The compound of the invention is applied for example by seed dressing, foliar spray, soil treatment, etc. The compound of the invention exhibits a sufficient efficacy when applied by methods which those skilled in the art usually employ. The rate of application of the compound of the invention and the concentration in which it is applied may vary depending upon the crop and disease to be treated, the degree of occurrence of the disease, the formulation of the compound, the method of application and various environmetal conditions. When it is sprayed, the suitable amount of the compound as an active ingredient is 50 to 5,000 g/ha, preferably 100 to 2,000 g/ha. When the formulation as a wettable powder or emulsifiable concentrate is diluted with water and sprayed, the ratio of dilution is preferably 200 to 10,000, preferaly 500 to 5,000.

The agricultural-horticultural fungicidal composition of this invention may be used or formulated together with another agricultural chemical such as another fungicide, an insecticide or a plant growth regulator, a soil conditioner, or a fertilizing sub- I,.c stance.

35 The compound of this invention may be applied 4 21 as such, but preferably in the form of a composition with a carrier (meant to include a solid or liquid diluent as well). The carrier, as used herein, means a synthetic or natural inorganic or organic substance which is incorporated in order to aid in the arrival of the active ingredient at a site to be treated and make it easy to store, transport and handle the compound as the active ingredient.

Suitable solid carriers include, for example, clays such as montmorillonite and kaolinite, inorganic substances such as diatomaceous earth, terra alba, talc, vermiculite, gypsum, calcium carbonate, silica gel and ammonium sulfate, vegetable organic substances such as soybean meal, sawdust and wheat flour, and urea.

Suitable liquid carriers include, for example, aromatic hydrocarbons such as toluene, xylene and cumene, paraffinic hydrocarbons such as kerosene and mineral oils, halogenated hydrocarbons such as carbon tetrachloride, chloroform and dichloroethane, ketones such as acetone and methyl ethyl keone, ethers such as dioxane and tetrahydrofuran, alcohols such as methanol, ethanol, 0 all propanol and ethylene glycol, dimethylformamide, dimethyl sulfoxide, and water.

4To enhance the efficacy of the compound of the 25 invention, adjuvants to be described below may be used o singly or in combination depending upon the type of the formulation, the situation of application, etc.

For purposes of emulsification, dispersion, spreading, wetting, binding and stabilization, there may be used, for enample, anionic surface-active agents such as ligninsulfonates, alkylbenzenesulfonates, alkylsulfuric ester salts, polyoxyalkylenealylsulfates and o polyoxyalkylenealkylphosphoric ester salts; nonionic surface-active agents such as polyoxyalkylene alkyl S 35 ethers, polyoxyalkylene alkyla:yl ethers, polyoxyalkylene o alkylamines, polyoxyalkylene alkylamides, polyoxyalkylene 1.

i a~ c 22 alkyl thioethers, polyoxyalkylene fatty acid esters, glycerin fatty acid esters, sorbitan fatty acid esters, polyoxyalkylene sorbitan fatty acid esters and polyoxypropylene/polyoxyethylene block polymers; lubricants such as calcium stearate and waxes; stabilizers such as isopropyl hydrogen phosphate and methyl cellulose, carboxy methyl cellulose, casein and gum arabic. These components should not be limited to the specific examples given above.

Usually, the amount of the active ingredient in the composition of this invention is 0.5 to 20 by weight for a dust, 5 to 20 by weight for an emulsifiable concentrate, 10 to 90 by weight for a wettable powder, 0.1 to 20 by weight for granules, and 10 to 90 by weight for a flowable agent. The amount of the carrier in the formulation is usually 50 to 99 by weight for a dust, 60 to 95 for an emulsifiable concentrate, 10 to 90 by weight for a wettable powder, to 99 by weight for granules and 10 to 90 for a flowable agent. The amount of the adjuvant is usually 0.1 to 20 by weight for a dust, 1 to 20 by weight for an emulsifiable concentrate, 0.1 to 20 by weight for a wettable powder, 0.1 to 20 by weight for granules, and 0.1 to 20 by weight for a flowable agent.

25 .The present invention also provides an agricultural-horticultural fungicidal composition comprising a dilient or a carrier and/or an adjuvant, and as a first active ingredient at least one amide derivative represented by the following general formula (I) o 0 00000 01 0 o 'a' 1 4 4u 0 Oo 'a 'a 00 0 R 2 R I

XA

Y43 Y ON~CH

N

wherein one of X and Y represents a sulfur atom and the, other represents a carbon atom, Z represents a nitrile or thioamide group, each

L

23 1 2 of R and R 2 represents a hydrogen atom, a halogen atom, an alkyl group having 1 to 6 carbon atoms, a halomethyl group or a phenyl group, and R 3 represents an alkenyl group having 2 to 6 carbon atoms, a haloalkenyl group having 2 to 4 carbon atoms, a furyl group, a thienyl group, an alkoxy group having 1 to 4 carbon atoms, an alkylthio group having 1 to 4 carbon atoms, an alkynyloxy group having 3 to carbon atoms, an alkynylthio group having 3 to carbon atoms, a pyrazolyl group, or an unsubstituted or halo-substituted phenyl group and as a second active ingredient at least one of acylalanine fungicides having the action of controlling plant diseases caused by Oomycetes, dithiocarbamate fungicides, N-haloalkylthioimide fungicides, inorganic copper fungicides, tetrachloroisophthalonitrile, dichlofluanide and fluazinam.

As the second active component used in this composition, examples of the acylalanine fungicides are metalaxyl, furalaxyl, benalayl, ofurace, oxadixyl and cyprofuram. Examples of the dithiocarbamate fungicides are zineb, maneb, mancozeb, polycarbomate and propineb.

Captan, captafol and folpet are examples of the N-halo- 0 25 alkylthioimide fungicides. Examples of the inorganic copper fungicides are cupric sulfate, basic cupric sulfate, basic cupric chloride and cupric hydroxide.

The above compound of this invention has both a preventive and a curative effect against a broad range of diseases in fruit trees and vegetables, and shows an excellent control effect against those plant diseases of which pathogenic fungi have acquired resistance to cono" ventional fungicidal chemicals. Furthermore the composition of this invention shows a sufficiently long S 35 residual effect and does not show phytotoxicity. It also 0 o has extremely low toxicity to warm-blooded animals and fish.

24 As an agricultural-horticultural fungicide, the composition of this invention shows a control effect against a wide range of plant diseases. Examples of plant diseases against which the cmposition of the invention shows an excellent control effect include ripe rot (Glomerella cingulata) anthracnose (Elsinoe ampelina) powdery mildew (Uncinula necator) rust (Phacospora ampelopsidis) and downy mildew (Plasmopara viticola) of grape; rust (Gymnosporangium yamadae), Alternaria leaf spot (Alternaria mali) fruit spot (Mycosphaerelli pomi) scab (Venturia inaequalis) and powdery mildew (Podosphaera leucotricha) of apple; anthracnose (Colletotrichum lagenarium) powdery mildew (Sphaerotheca fuliginea), gummy stem blight (Mycosphaerella melonis) downy mildew (Pseudoperonospora cubensis), Phytophthora rot (Phytophthora melonis), scab (Cladosporium cucumerinum) and bacterial spot (Pseudomonas lachrymans) of cucuribit; early blight (Alternaria solani) leaf mold (Cladosporium fulvum) Phytophthora rot (Phytophthora capsici) late blight (Phytophthora intestans) and powdery mildew (Erysiphe cichoracearum) of tomato; Alternaria leaf spot (Alternaria japonica), white spot (Cercosporella brassicae) and downy mildew of cruciter; rust (Puccinia alli) and downy mildew (Peronospora destructor) of green onion; downy mildew (Peronospora spinacie) of spinach; scab (Elsinoe glycines), purple speck (Cercospora kikuchii) and downy mildew (Peronospo rtmanshurica) of soybean; anthracnose (Colletotrichum lindemuthianum) and rust (Uromnyces appendiculatus of kidueybean; downy mildew (Peronospora viciae) of field beans; black shank (Phytophthora nicotiana var. nicotiana) of tobacco; early blight (Alternaria solani) and late blight (Phytophthora infestans) or potato;i downy mildew (Pseudoperonospora Shumuli) of hop; Phytophthora rot (Phytophthora cinnamoi) 3 of pineapple; Phytophthora blight of green pepper (Phytophthora capsici); powdery mildew (Sphaerotheca 25 humuli) and red stele (Phytophthora fragaric) of strawberry and grey mold (Botrytis cinerea), sclerotinis disease (Sclerotinia sclerotiorum) and damping-off (by Phythium, etc.) of various crops.

The co'ipound of the invention is applied for example by seed dressing, foliar spray, soil treatment, etc. The compound of the invention exhibits a sufficient efficacy when applied by methods which those skilled in the art usually employ. The rate of application of the compound of the invention and the concentration in which it is applied may vary depending upon the crop and disease to be treated, the degree of occurrence of the disease, the formulation of the compound, the method of application and various environmental conditions. When it is to be sprayed, the suitable amount of the compound as an active ingredient is 50 to 5,000 g/ha, preferably 100 to 2,000 g/ha. When it is to be sprayed as a wettable powder or emulsifiable concentrate diluted with water, the ratio of dilution is preferably 200 to 10,000, preferably 500 to 5,000.

The agricultural-horticultural fungicidal composition of this invention may be used, or formulated, together with another agricultural chemical such as another fungicide, an insecticide or a plant growth regulator, a soil conditioner, or a fertilizing substance.

The compound of this invention may be applied as such, but preferably in the form of a composition with 0, a carrier (meant to include a solid or liquid diluent as well). The carrier, as used herein, means a synthetic or 6oon natural inorganic or organic substance which is incorporated in order to aid in the arrival of the active ingredients at a site to be treated and make it easy to mo store, transport and handle the compound as the active S 35 ingredients.

S" Suitable solid carriers and liquid carriers and i r

;I-

-i i l 26 adjuvants may be the same as those exermplified above.

Usually, the amount of the active ingredients in the composition of this invention is 0.5 to 20 by weight for a dust, 5 to 20 by weight for an emulsifiable concentrate, 10 to 90 by weight for a wettable powder, 0.1 to 20 by weight for granules, and 10 to by weight for a :lowable egent. The amount of the carrier in the formulation is usually 50 to 99 by weight for a dust, 60 to 95 by weight for an emulsifiable concentrate, 10 to 90 by weight for a wettable powder, 80 to 99 by weight for granules and to 90 by weight for a flowable agent. The amount of the adjuvant is usually 0.1 to 20 by weight for a dust, 1 to 20 by weight for an emulsifiable concentrate, 0.1 1 to 20 by weight for a wettable powder, 0.1 to 20 by weight for granules, and 0.1 to 20 by weight for a flowable agent. The ratio of the fungicide as the second active ingredient to the amide derivative of the invention can be freely changed between 0.1 and The processes for producing the amide derivatives of general formula provided by this invention will be specifically illustrated by the following Synthesis Examples.

SYNTHISIS EXAMPLE 1 25 Synthesis of N (alpha-cyanofurfuryl)-2-chloroamide (compound No. 37):- 8.8 g of 2-chloro-4-methylthiazole-5-carboxylic acid was suspended in 7 ml of thionyl chloride, and one drop of N,N-dimethylformamide was added. The mixture was heated under reflux for 1 hour, and then the excess of thionyl chloride was evaporated under reduced pressure.

Benzene (10 was added, and the mixture was .apoated under reduced pressure. This procedure was repeated three times to give 9.7 g of 2-chloro-4-methylthiaz)le- 5-carboxylic acid chloride which was used in the following reaction without purification.

I) I C C C C *i S i i 4 4i

L_

11 27 The 2-chloro-4-methylthiazole-5-carboxylic acid chloride (1.6 g) was suspended in 30 ml of pyridine, and 1.3 g of alpha-2-furyl)-alpha-aminoacetonitrile hydrochloride was added. The mixture was stirred at room temperature for 2 hours. After the reaction, the reaction mixture was filtrated. The filtrate was concentrated, and the residue was purified by silica gel column chromatography. Elution with hexane ethyl acetate gave 1.79 g (vield 75.2 of the desired N-(alpha-cyanofurfuryl)-2-chloro-4-methylthiazole-5-carboxylic acid amide.

SYNTHESIS EXAMPLE 2 Synthesis of N-(alpha-cyanofurfuryl)-2,4acid amide (compound No.

9.30 g of 2,4-dimethylthiazole-5-carboxylic acid was suspended in 90 ml of toluene, and 15.0 g of phosphorus pentachloride was added. The mixture was refluxed for 1 hour. Under reduced pressure, the resulting phosphorus oxychloride and the toluene were evaporated to give 2,4-dimethylthiazole-5-carboxylic acid chloride which was used in the following reaction without purificao tion.

S, In 120 ml of ethylacetate were dissolved 6.2 g ,O of alpha-(2-furyl)-alpha-aminoacetonitrile and 6.0 g of o 25 triethylainine, and with stirring, the 2,4-dimethylthiazole- 5-carboxylic acid chloride was added dropwise to the solution, and the mixture was stirred at room temperature for 1 hour. Water (150 ml) was added, and the precipitated triethylamine hydrochloride was dissolved. The ethyl acetat, layer was separated, washed with water, and dried over sodium sulfate. The dried ethyl acetate layer was distilled under reduced pressure to remove the solvent.

The residue was recrystallized from isopropyl ether to give 11.65 g (yield 90.0 of the desired N-(alpha-cyanofurfuryl)-2,4-dimethylthiazole-5-carboxylic acid amide.

4.

I

-28 SYNTHESIS EXAMPLE 3 Synthesis of N-(alpha-cyanofurfuryl)-2,4-diacid amide (compound No. 12) In accordance with the m~dof Synthesis Example 2, 2,4-diethylthiazole-5-carboxylic acid and phosphorus pentachioride were reacted to give 2#4-diacid chloride quaintitatively.

The 2,4-diethylthiazole-5-carboxylic acid chloride was used in the following reaction without purification.

2.80 g of alpha-(2-furyl)--alpha-aminoacetonitrile arid 6.0 g of triethyj.amine re dissolved in ml of ethyl acetate, and with stirring, 2.1 g of the 2,4-diethylthiazole-5-carboxylic acid chloride was added dropwiser and the mixture was stirred at room temperature for 1 hour. Water (150 ml) was added, an~l the precipitated triethylamine hydrochloride was dissolved. The ethyl acetate layer was separated, washed with water andl dried over sodium sulfate. The dried ethyl acetate layer was evaporated under reduced pressure to remove the sol- 'a ait A a a a 'a a a a a ao a o 0 a 0 Ia a a a a a I 0* a.

I a alit eIIIaaI *1 a I I- 100110 *#0 vent. The residue was recrystallized from n-hexane to give 2.41 g (yield 80.0 of the' desired N-1(alphacyanofurfury1)';2,4-dimethylthiazole-5-carboxylic acid am ide.

SYNTHESIS EXAMPLE 4 25 Synthesis of N-(alpha-cyanofurfuryl)-2,4dimethylthiazole-5-carboxylic acid amide (compound No. 2) by using a mixed acid anhydride:- 4.71 g of 2,4-dimethylthiazole-5-carboxylic acid was suspended in 70 ml of tetrahydrofuran, and 6.67 30 g of tr~ethylamine was added. The mixture was stirred.

Whil.e it was cooled to -10 to OC 4.10 g of n-butyl chloroformate was added, and the mixture was stirred at this temperature for 30 minutes, a(,nd then 4.03 g of alpha-(2-furyl)-alpha-aminoacetoni\ rile hydrochloride was 35 added. The mixture was stirred at room temperature for hou,rs, and then left to stand overnighnt. The prec1.pitate I

I

U.

29 was separated by filtration and distilled under reduced pressure to remove the solvent. The residue was purified by silica gel column chromatography. Elution with hexane/ethyl acetate gave 4.20 g (yield 53.6 of the desired N-(alpha-cyanofurfuryl)-2,4-dimethylthiazole-5carboxylic acid amide.

SYNTHESIS EXAMPLE Synthesis of N-(alpha-cyanofurfuryl)-2,4acid amide (compound No. 2) by the CDI method:g of alpha-(2-furyl)-alpha-aminoacetonitrile hydrochloride and a mixture of 3.70 g of a 50 aqueous soution of NaOH and 50 ml of isopropyl ether were stirred at 40 oC for 1 hour under a nitrogen gas. The isopropyl ether layer was separated. Separately, while 4.71 g of 2,4-dimethylthiazole-5-carboxylic acid and 4.88 g of carbonyldiimidazole (CDI) were stirred in 50 ml of methylene chloride, the alpha-(2-furyl)-alpha-aminoacetonitrile in isopropyl ether was added dropwise under ice cooling. The mixture was left to stand overnight at room temperature, and distilled under reduced pressure to remove the solvent. The residue was dissolved in ethyl acetate, separated, washed with water, and dried over sodium sulfate. The ethyl acetate layer was distilled 25 under reduced pressure to remove the solvent. The re- S o sidue was recrystallized from isopropyl ether to give 5.51 g (yield 70.4 of the desired N-(alpha-cyanofurfuryl)-2,4-dimethylthiazole-5-carboxylic acid amide.

N SYNTHESIS EXAMPLE 6 Synthesis of N-(alpha-cyanofurfuryl)-2,4acid amide (compound No. 2) by the DCC method:- ~3.0 g of alpha-(2-furyl)-alpha-aminoacetonitrile hydrochloride and a mixture of 70 g of a 50 aqueous solution of NaOH and 30 ml of methylene chloride were stirred at 40 C for 1 hour under a nitrogen gas.

44 30 Then, the methylene chloride layer was separated. Separately, while 2.50 g of 2,4-dimethylthiazole-5carboxylic acid and 3.10 g of dicyclohexylcarbodiimide (DCC) were stirred in 50 ml of methylene chloride, the alpha=(2-furyl)-alpha-aminoacetonitrile was added dropwise under cooling with ice water over the course of 1 hour. After the addition, the mixture was stirred for 1 hour under ice cooling, left to stand overnight at room temperature, and distilled under reduced pressure to remove the solvent. The residue was dissolved in ethyl acetate, separated, washed with water and dried over sodium sulfate. The ethyl acetate layer was distilled under reduced pressure to remove the solvent. The residue was purified by silica gel column chromatography.

Elution with hexane/ethyl acetate gave 1.85 g (yield 47.3 of the desired N-(alpha-cyanofurfuryl)-2,4acid amide.

SYNTHESIS EXAMPLE 7 Synthesis of N-(alpha-cyanofurfuryl)-3methylisothiazole-4-carboxylic acid amide (compound No.

o 32):- 1.2 g of alpha-(2-furyl)-alpha-aminoacetonitrile hydrochloride was dissolved in 10 ml of pyridine, and with stirring at room temperature, 1.1 g of 3methylisothiazole-4-carboxylic acid chloride was added S dropwise. After the dropwise addition, the mixture was u stirred for 1 hour, and distilled under reduced pressure to remove pyridine. The residue was dissolved in ethyl f acetate, separated, washed with water, and dried over sodium sulfate. The ethyl acetate layer was distilled under reduced pressure to remove the solvent. The residue was purified by silica gel column chromatography.

i Elution with benzene-ethyl acetate gave 1.2 g (yield of the desired N-(alpha-cyanofurfuryl)-3-methyl- "oo. 35 isothiazole-4-carboxylic acid amide.

I

4 4,- 31 SYNTHESIS EXAMPLE 8 Synthesis of N-(alpha-cyanofurfuryl)-3-methylacid amide (compound No. 34):g of alpha-(2-furyl)-alpha-aminoacetonitrile hydrochloride was dehydrochlorinated with sodium hydroxide in ethyl acetate by the same method as in the above Synthesis Example 6. Pyridine (2.5 g) was added, and furthermore, an ethyl acetate solution of 4.0 g of acid chloride was added dropwise. After the addition, the mixture was stirred for 1 hour. The reaction mixture was washed with water, dilute hydrochloric acid and a dilute aqueous solution of so6du' bicarbonate. Sodium sulfate, and active carbon were added to dehydrate and decolorize the reaction mixture. The solvent was removed under reduced pressure, and the residue was washed with ethyl ether to give 4.5 g (yield 74 of the desired N-(alpha-cyanofurfuryl)-3acid amide, SYNTHESIS EXAMPLE 9 Synthesis of N-(l-cyano-3-methyl-2-butenyl)acid amide (compound No.

36):- To a mixture of 30 ml of water and 30 ml of ethyl ether were added 3 ml of 28 aqueous ammonia, g of sodium cyanide, 4.5 g of ammonium chloride and 0.5 g of triethyl benzyl ainmoniuin chloride, and the mixture was cooled to 5 0 C. With stirring a solution of 2.8 g of 3-methyl-2-butenal was added dropwise. After the dropwise addition, the mixture was continuously stirred at 30 to 20 °C for 5 hours. The ether layer was separated, washed with water and dried over sodium sulfate to give an ether solution of l-cyano-3-methyl-2-butenylamine.

Triethylamine (1.0 g) was added to the solution, and with stirring at room temperature, an ethyl acetate solution of 1.1 g of 3-methylisothiazole-5-carboxylic acid chloride was added dropwise. After the additiont the

*I

i 1 o uo o 0 1 0i 0 001 32 mixture was stirred for 1 hour, washed with water, and distilled under reduced pressure to remove the solvent.

The residue was purified by silica gel column chromatography. Elution with benzene/ethyl acetate gave 1.0 g (yield 63 of the desired N-(l-cyano-3-methyl-2acid amide.

SYNTHESIS EXAMPLE Synthesis of N-(alpha-cyanobenzyl)-2-methylacid amide (compound No. 1.2 g of alpha-benzyl-alpha-aminoacetonitrile hydrochloride was suspended in 20 ml of ethyl acetate, and 7 ml of 10 NaOH was added dropwise at a temperature below 10 The mixture was stirred at this temperature for 10 minutes, and an ethyl acetate solution of 0.8 g of 3-methylisothiazole-5-carboxylic acid chloride was added dropwise at 0 After the addition, the mixture was stirred for 30 minutes. The ethyl acetate layer was washed with water, and distilled under reduced pressure to remove the solvent. The residue was purified by silica gel column chromatography. Elution with benzene/ethyl acetate gave 1.0 g (yield 77 of the o desired F, carboxylic acid amide.

SYNTHESIS EXAMPLE 11 i 25 Synthesis of N- alpha-cyano-alpha-(l-pyrazolyl)acid amide (compound No. 46):- 0.7 g of N-(cyanomethyl)-3-methylisothiazole- 5-carboxylic acid amide was dissolved in 30 m 1 of ethyl acetate. Bromine (0.8 g) was added and the mixture was stirred for 30 minutes, and then cooled over an ice oath.

A mixture of 0.3 g of pyrazole, 1.0 g of triethylamine and 5 ml of ethyl acetate was added to the reaction mixture with stirring. The mixture was stirred for minutes. The ethyl acetate layer was washed with water and distilled under reduced pressure to remove the k] 1 4 33 solvent. The residue was purified by silica gel column chromatography. Elution with benzene/ethyl acetate gave 0.75 g (yield 78 of the desired N-[alpha-cyano-alphaacid amide.

SYNTHESIS EXAMPLE 12 Synthesis of N-[alpha-cyano-alpha-(l-pyrazolyl)methyl]-2,4-dimethylthiazole-5-carboxylic acid amide (compound No. 38);- Synthesis of N-cyanomethyl-2,4-dimethylthiazoleacid amide:- A mixture of 10 g of 2,4-dimethylthiazole--bcarboxylic acid, 13.6 g of thionyl chloride and 70 ml of toluene was cooled with ice, and with stirring, 8.4 g of N,N-dimethylformamide was added. The mixture was stirred for 3 hours at 3 to 5 oC and then for 1 hour at 20 oC, and 200 ml of toluene and 37 g of triethylamine were added. An ethyl acetate solution of aminoacetonitrile prepared from aminoacetonitrile sulfate using ethyl acetate and NaOH was gradually added to the reaction mixture being cooled with ice. The mixture was stirred at room temperature for 1 hour. The reaction mixture was pouued into water and extracted with ethyl acetate. The ethyl acetate layer was washed with water, dried, and distilled under reduced pressure to remove the solvent.

The residue was purified by silica gel column chromatography. Elution with hexane/ethyl acetate gave 6.6 g (yield 53 of N-cyanomethyl-2,4-diethylthiazole-5carboxylic acid amide.

30 Synthesis of N-[alpha-cyano-alpha-(l-pyrazolyl)methyl]-2,4-dimethylthiazole-5-carboxylic acid amide:- 1.0 g of N-cyanomethyl-2,4-dimethylthiazoleacid amide was dissolved in 30 ml of ethyl acetate. Bromine (03 ml) was added and the mixture was 35 refluxed until the dark brown color of bromine disappeared. The reaction mixture was cooled over an ice no C9 0 0 0 4 L4 4D 4 1 4 4 04 4444 1 4444 4 4 i 4 I S«t j- .li-~ILY1.-. 34 bath, and 0.5 g of pyrazole, 2.0 g of triethylamine and ml of ethyl acetate were added at the above temperature. The mixture was stirred at room temperature for 2 hours. The reaction mixture was poured into water, and extracted with ethyl acetate. The ethyl acetate layer was washed with water, dried and distilled under reduced pressure to remove the solvent. The residue was purified by silica gol column chromatography. Elution with hexane/ethyl acetate gave 0.74 g (yield 54.9 of the desired N-[alpha-cyano-alpha-(l-pyrazolyl)methyll-2,4acid amide.

SYNTHESIS EXAMPLE 13 Syntehsis of N-(alpha-cyano-alpha-ethoxymethyl)-2,4-dimethylthiazole-5-carboxylic acid amide 1 (compound No. 39):g of N-cyanomethyl-2,4-dimethylthiazole-5carboxylic acid amide was dissolved in 30 ml of ethyl acetate. Bromine (0.3 ml) was added and the mixture was heated under reflux until the dark brown color of bromine 2 disappeared. The reaction mixture was cooled over an ice bath, and 1.0 g of ethanol, 2.0 of triethylamine and ml of ethyl acetate were added at the above temperature.

The mixture was stirred at room temperature for 2 hours.

The reaction mixture was poured into water and extracted with ethyl acetate. The ethyl acetate layer was washed with water, dried, and distilled under reduced pressure to remove the solvent. The residue was purified by silica gel column chromatography. Elution with hexane/ethyl acetate gave 0.53 g (yield 43.1 of the desired N-(alpha- cyano-alpha-ethoxymethyl)-2,4-dimethylthiazoleacid amide.

SYNTHESIS EXAMPLE 14 Synthesis of N-[(alpha-thiocarbamoyl)furfuryl] -3-methylisothiazole-5-carboxylic acid amide S(compound No. 47):- 1.0 g of N-(alpha-cyanofurfuryl)-3-methyl- 0,".n SCn 4 I 1 i-: _I~ILI~-U~~CICr s 35 acid amide was dissolved in ml of tetrahydrofuran, and 0.6 ml of triethylamine was added. With stirring at room temperature, hydrogen sulfide gas was introduced into the mixture. Five hours later, the reaction solvent was evaporated under reduced pressure. Water was added to the residue. The precipitated crystals were separated by filtration to give 1.1 g of the desired N-[(alpha-thiocarbamoyl)furfuryll-3-methylacid amide.

Table 1 below shows typical examples of the amide derivatives of general formula provided by this invention. The designations and in the column of "Process" means the processes and respectively, described above.

0 a1 4 a i Li Table 1 NMR (100 MHz, S) (CDC1 2.72(3H, 6.24-6.660(H1, mn), 7.34-3.49(l1, im), 7.97(111, broad d, J=711z), 8.04(111, s) (CDC1 )2.61(3H, 2.64(0H, 6.34 7.48(11, in), 7.96(11, d, (CDCl 1.84(61, 2.71f6H, 5.34(111, d, J=9.011z), 5.68(11, t, J::8.OHz), 6.16 (1H1, d, J=8.OHz) (ClC 2.66(61, 6.42(11, d, J=9.OHz), 6.98(311, mn), 7.34(11, d, J=8.OHz), 7.38 (11, d,,J=9.011z) (Q)C1 2.60(6H1, 6.18(11, d, J=9.OHz), 6.68d11, J=9.OHz), 7.0-7.111, mn), 7.28-7.44 (2H, mn) (CC 2.61(61, 6.18(111, d, J=9.OHz), 6r.81d11, d, 7.28-7.52(5H1, in) -to b continued i 1 Table 1 (continued) N CH3 0(CDC1 2.720HB, 6.26(lH, d, J=8,.tz), 7 1 CN oil 6.36RH, 6.54(1, broad d, J=41z), 6.95 s d, J=8.1z), 7.43(1H, broad d, J=4Hz), 8.65(11, s) (CDC1 2.620HB, 6.16UHr d J=.OE~z) 8 g) oil 7.2-7.5(5, 8.46(11, s) (a) 3 0 (CDC1 1.40(3H, t, J=8Hz), 2.70(3, s), 99-102 3.00(1, q, J=8Hz), 6.36(lH, broad d, J=8Hz),

C

2 5 s 6.4-6.7(2H, 6.78(lH, broad d, J=8Hz), 7.42(1H, m) (CDC1 1.34(3, t, J=7Hz), 2.68(3H, 2.98 90.5-91.6 (2H J=711z), 6.41(1H, d, J=8Hz), 6.61(1, broad d, J=81z), 6.96-7.12(11, 7.23-7.48 (21, m) (CDC1 3 1.36(3H, t, J=7z), 2.66(3H, 2 96 11 oil (21, q, J=71z), 6.22UH, d, J=8Hz), 6.46(11, 00 broad d, J=8z), 7.12-7.60(51, m) (CDC1 1.30(31, t, J=8Hz), 1.38(3, t, J=81z), 12 C 114.5-115.5 2.98(E.H, q, J=8Hz), 3.09(2H, q, J=8Hz), 6.28 (1H, d, J=8ffz), 6.40(11, 6.56(21, m) 7.48 (1H, m) s(CDCl 1.310Hi t, J=8HZ) 1.390hl t, J=8HZ), 13 117-118 2.97d11, q, J=8Hz), 3.05(2H, q, J=8Hz), 6.29 d, J=9Hz), 6.74111, broad d, J=9Hz), 7.00 (1H, 7.2-7.4(2H, m) to be continued 2

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I-i 7~3 0 ;OiC r, ri p Z 1-

C

C LD IC CC L *D O C ,C 1 001 ,OQ i 1 91 4 4 a 444 4 *44 46 Table 1 (continued) N CA (CDC1 1.2603H, t, J=8Hz), 1.34(3, t, 14 N 79-81 J=8H 2 2.2(2H1, q, J=8Hz), 3.00(2H, q, J=8Hz), s ~6.211H, d, J=9Hz) 667 d, J=gHz) 7.20-7.50(5M, broad s) (C)Cl 1.02(3H, t, J=7Hz), 1.80(2H, m, J=7Hz), n-C A 1 oil 2.68(]H, 2-91(2H, t, J=71Wz), 6.31(lH, d, Wi J=8Hz), 6.42, 6.59, 7.47(each 1H, 6.80 broad d, J=8Hz) s (CDC1 1.0003H, t, J=7Hz) 1.78(2H, m, J=7Hz), 16 oil 12.66 3H, 2.89(211, t, J=7Hz), 6.41(11, d, J=8Hz), 6.62(1H, broad d, J=8Hz), 7.0-7.4 (3H, m) S2 5 (CDCL 1.303H, t, J=71z), 2.69(3H, s), 17 CU 0 oil 3.47(H, q, J=7Hz), 6.29(1H, d, J=8Hz), 6.29-6.72(3H1, 7.28-7.711H, m) S (CDC1 1.20(30, t, J=8Hz), 2.67(311, 2.96 18 124.5-125,: (21, 1, J=8Hz), 6.53(11, d, J=7Hz), 7.00-7.72 W (3H, 9.6(11, broad d, J=7Hz) (QC\ 1-27(30, t, J=7Hz), 2.67(3, 3.03 19 11i-112 J=7Hz), 6.22(11, d, J=8Hz), 6.66(11, broad d, J=8Hz), 7.20-7.64(5, m) N 11-C7-1 (CDC1 0.96(3, t, J=8Hz), 1.74(2H, m, e0 117-418 (1 ,d 0(3H, 6.4, 3.02(2, t, J=8Hz) 1, 6.32 M dl, J=Hz), 6.45, 6.60, 7.70(each 1, m), 6.88(11, broad d, J=8gz) to be continued

F

0 0) 0 00 000 0 Ca 0 CC 0r 00 Table 1 (continued) N n-C P 7 CH3 I'

S:

01 117.5-119 (CDCJ 0.9607.5(4 J=8z) 1.54(2Hn) J=8Hz), 2.685j]H, 3.01(2H, t, J=8Hz), 6.44UHi d, J=V~Z) 6.90-7.50W8, :m) (C1C1 0.93(31, t, J=8Hz) 1.70(2H, mi J=811z), 22 of 93-94 2.66(h, 2.98(2H, t, J=8Hz), 6.25(1, d, J=9Hz), 6.84(1, broad d, J=9Hz), 7.28-7.74 (51, m) CF 3 (CIC1 3 2.77(3H, 6.23(11, d, J=81z), 6.45 23 CHU7 I 105-107 (1H1, 6.62(1H, in) 6.93(1, broad d, J=81z) 7.50 n) (CDC1 2.76(30, 6.39(11, d, J=8Hz), 24 oil 6.9C-3.13 (2H, mi), 7.36-7.48(2H, i k N C 2(CDC1 1.34(3, t, J=8Hz), 3.20(21, j=81z), 98.5-99.0 6.30(Ii, d, J=8Hz), 6.42(11, mn), 6.60%i'- in, W, -00/ 6.72(1., broad d, J=81z), 7.48(1U, uO, 7.74 s) 215 0 (aD 3 2.743, 6.26(1, d, J=8Hz), 26 Qj147-151 6.I-6.7(4H, 7.3-7.5(31, 7.8-7.9(21, n fa) to be continued -r

K__

Tatal- 1 (continued) (a)Cl )2.640H1, si, (1H1, broad d, J=811z) 6.26(111, d, J=811z) 6.8 Vn) .9.24 (CDC1 2.73(3OH, s) 6.25 d, J=811z) 6.056 (1H, Aroad d, J=811z) 7 36-7.62 (8H, in) 7 A2-7.97 (2H, mn) (CDC1 2.72(3H1, 6.43(11, d, J=811z), 6.45-:.68(2H, in), 7.32-7 87(6H1, 9.78(11, broad d, J=811z) (C)C1 2.73(3H, 6.51(11, d, J=7Hz), 6.83-.79M81, Wn, 9.82(1H, broad d, J=7Hz) (CDC1 2.70(3H, 6.25(11, d, J=711z), 7.04-.74 (10F1, m) 9.67(~in, broad d, J=711z) (C)C1 2.62(3H, 6.26(11, d, J=6Hz), 6.38d11, t, J=211z), 6.54(1H, d, J:=2Hz), T.44 to be contcinued i 4. 4 St. a Ot- II O C D ~r

LI

OWO L1

LP~O

o;

~LCI-

o 44 4 4 tO 4 004~ a Table 1 (continued)

I-H

3ICH (CDCl 1.84(6H, 2.68(3, 5.34 d, 33 -CH 4 13 CN oil J=81z?, 5.70(11, t, J=81z), 7.30(11, d, J=81z), S ~21 3 9.08(111, S) N (DMSO-d-) 2.87(111, 6.44(11, d, J=81z), 34 136-137 6.50(lf1? t, J=21z), 6.62(1, d, J=2Hz), 7.74 s d, J=21z), 7.76(1, 10.02(11, d, (J=8Hz) C)MSOd 6 )2.54(3, 6.40(111, broad), 7.4-7.7 129-131 (5H, 7.8411, 10.0(11, broad) CE (EX4SO-d 8(6H, d, J=2Hz), 2.4803H, S), 6 -CH123-125 5.3-5.8t21,m), 7.74(11, 9.53(IH, d, J=8E1z) N C3 )(CDCI 2.550H, s) .24UH, djJTffiz), 37 c-\/90-91 6.55M, 7.52(lH8, 8.06(lH, d, J=8Hz)

S-Y'

H33 C7A -V

-NJ

K

140-141 (CDC1 2.67(3, 6.30-6.40(1H, 7.28 (11, J=811z), 7.60-7.66(11, 7.72-7.80 (11, 8.30(1, d, J=81z) to be continued

I

I I W- il Li L. I a a r tn c a

L

C L

L-L

0 0 00 0 0 a a

I"OC

s r -rrr te_ a n ao: i oar, a 4 U Table 1 (continued) CT1 (CDC1 1.30(3, t, J=7Hz), 2.70(3H, s), 39 H()Cp5 CN 89-90 2.73(]H, 3.71(2H, q, J=7Hz), 6.10(1, d, 32 0 J=1OHz) 6.95(1H, d, J=lOHz) (cDCl 2.25-:2.59(lH, m) 2.71 (6H, 4.31 -OCHC=C1 oil (2H, A. J=31Fz), 6.31(1H, d, J=9Hz), 7.04(11, d, J=9Hz) (CDCl 1.37(3, t, J=8Hz), 2.68(1, 2.70 41 -SC H oil (311 2.87(2H, q, J=8Hz), 6.15(11, d, J=9Hz) 6.96(1M, d, j91z) (CDC1 0.93(3, t, J=711z), 1.80(2H, m, J=71z), 42 -OC 3

H

7 oil 2.68(IH, 2.91(211, t, J=7Hz), 6.31(11, d, J=8Hz), 6.42, 6.59, 7.47(each 1H, 6.80 broad d, J=81z) (CDC1 2.66(3H, 2.68(3, 3.38(3, s), 43 -CCH3 oil 5.95(if, d, J=9Hz), 71.08(11, d, J=91z) (CDC1 1.36(3, d, J=6Hz), 1.39(3, d, J=6Hz), 44 -9CC3N 1 105-106 /:2.6543HI s, 2-680HB, 3.25(lH, m, J--6Hz) 6. d, J=911z), 7.03(11, broad d, J=911z) to be cort't u& a a 0* e a 14 (DMS-d )2.56(3OH, s) 6.40 (1H1, t, J=2Hz) 7.64 (1H, d,6J=811z), 7.70(11, d, J=2Hz), 7.86(11, 7.94(111, d, J=211z), 10.96(11, d, J=811Z)

(MSO-

6 2.60OH, s) 6.40 (1H1, t, J=211z) 7.60 (1H1, d,6J=8Hz), 7.66(11, d, J=2Hz), 7.96(11, di, J=2fLz). 9.62(1H, 10.5G%111, di, J=811z) (DMSO-d 2.48(3H, 5.92(1H, d, J=7.511z), 6.3-6.2(2, m, 7.62(11, 7.87(11, s), 9.13(11, di, J=7.511z), 9.54(111, 9.82(11, s) (DMSO-d 2.58(31, 2.63(31, 5.94(111, d, J=8.HzV, 6.41(2H1, 7.57(111, 8.16(111, d, J=8.SHz), 9.60(11, 9.98(111, s) (CDC1 2.70(3H, 4.9(2H1, 6.22(11, di, J=811 2 6.32-6.64(21, in),.7.08(111 bd, J=8Hz), 7.40-7.48(11, mn) (CDC1 1.24(6H1, d, J=711z), 2.63(31, 3.63 (11, Art, J=7Hz), 6.16(11, d, J=811z), 6.16-6.68 (2H1, 6.55(11, bd, J=811z), 7.16-7.39(11, mn) -ii Si 1~ w to be continued Table 1 (continued) (CDC1 1.28(6H, d, J=7Hz), 2.64(3H, 3.72 1H1, q J=711z), 6.33(11, d, J=811z), 6.60(11, bd, J=8Hz), 5.75-7.2231, in) (CDC1 1.21(6H1, d, J=711z), 2.57(3H, 3.61 bd, J=811z) 7.10-7.24 (5H, mn) (CIJC1 2.68(3H, 6.23(11, d, J=811z), 6.l2-:62(2H, 7.20-7.44(11, 7.90(11, bl), 8.01(11, s) (aCD1 1.27(0H, t, 1.81(6H1, 2.65 J=8Hfz), 5.60(111, bd, J=811z), 6.48(1H, bd, J=811z) ((C)C1 1.32(3H, t, J= 2.7503H, 3.11 J=811z), 7.5-7.8(8H1, 7.88(11, mn) (CDC31 1.30(31, t, J=811Z), 2.75(3H, 3.10 (2H, i, J=811z), 6.44(11, d, J=811z), 7.20(111, J=811z), 6.62(4H1, mn) 'Lo be continued- B C B OA

O

LI D D CI ~O L1 aDB C D Be 7 'J Die

BQ

00 OLD (O 5r O O O P 9 allLi~ 0-010

L

Table 1 (continued) 'N C146-4 (CDCl 3 1.29(3H t, J=8Hz), 2.73(30, 3.08 57 CH 3 Y r E C 01 146-148 UH, q, J=8Hz), 6.40( d, J=8Hz), 7.08(11, J=gHz), 7.64(4H, s) N 0 (CDC1 5.301H, d, J=8Hz), 6.1-6.62(2H, m), 58 oil 7.l8-i.46UH, mn), 8.14(H bd, 3=8Hz), 8.35 M, (11 8.86(11, s) C H N 2 5 0 (CDC1 1.28(3, t, J=8Hz), 1.37(6H, d, J=7Hz), 59 i-C YO 88-89 3.03(H, q, J=8Hz), 3.18(1, sx, J=7Hz), 6.24 s (1H, 3=7Hz), 6.33(1, d, J=7Hz), 6.16-6.24 m) 7.28-7.52(1H, m) (CDCl 1.30(3H, t, 3=8Hz), 1.39(61, d, 3=7Hz), 135-136 3.06(H, q, J=8Hz), 3.25(1, qt, J=7Hz), 6.41 (211, singlet like), 6.92-7.46(3H, m) (CDC1 1.293H, t, J=8Hz), 1.38(6H, d, J=6Hz), 61 n 115-116 3,05(H, q, J=8Hz), 3.32(11 qt, J=6Hz), 6.25 (2H, singlet like), 7.20-7.60(5H, m) DCl 1.28(3, t, 3=7Hz), 1.43(91, 3.05 62 t-C 4 11~~ H\qJ 108.5-109.5 (2f, J, 3=7Hz), 6.24(1H, 6.10-6.58(3H, in), 1 7.20-7.46(1H, mi to be continued i

N.

-1 o-i

"F

rC- P- rl i" LI X P i"

I

L

.i a 1 s. s a i;o R ail r ~C-rZI 9 Orlr e~ Table 1 (continued) NI (CDC1 1.29(3H, t, J=8Hz), 1.43(9H, 3.06 63 t-C4 N 145-146 (21,a, J=8Hz), 6.39(2H, singlet like), 9 5 -k 6.90-7.44(3, m) (cDC1 1.30(3H, t, J=8Hz), 1.44(9H, 3.08 64 126-127 (211 J=8Hz), 6.22(21, singlet like),' 7.20-7.64(5H, m) N 25 (CDCl) 1.26(3, t, J=7Hz), 2.65(3H, .97 CH 3 118-120 6.28(11H, d, J=8Hz), 6.46(11, S bd, J=8z), 7.0-7.6(4H, m) N Cl 0 (1H, d, J=811z), 6.02-6.68(2H1, Wn, 66 Ssemi-solid 7.llH, bd, J=81z), 7.20-7.44(11, m) C1 N 0 (cDCl 2.89(3, 6.36(1, d, J=8Hz), 67 106-107 6.36-:.68(2H, 7.36-7.56(11, 8.14(1H, bd, J=8z), 8.51(11, s) N S (CC1 2.86(3, 6.44(1, d. J=8Hz), 68 101-104 6.90-3.10(1H, 7.22--7.45(2H, 8.16(1H, S J=8Hz), 8.44(11, el to be continued I 1 1

-L-

I CIC--- 1-1-

O

I 1 rll C e *Lir -rP

I

tit o

O

h, b9*

D

r, ODP D r OICIP 5; Table 1 (continued)

N

r 21 -0 94-94.5 (CDCl 2.88(3, 6.31(11, d, J=8Hz), 7.30-3.68(5H, im), 8.15(1, bd, J=8Hz), 8.46

S)

N C3 s (CDC) 2.65(3, 6.42(1, d, J=8Hz), 6.76 128.0-129.0 (11, a, J=81z), 7.0-7.2(2H, 7.4(1, s) N (73 0 (CDC 2.70(3, 6.31(1, d, J=81z), 6.52 71 Br-( N 92.5-93.0 H(11, a, J=3.0, 1.0Hz), 6.55(1, d, 1=3.0Hz), 6.83(11, d, J=8Hz), 7.55(11, d, J=1L) s (CDC1 2.67(31, 6.41(11, d, J=81z), 6.77 72 N t 131.5-132.0 H(11, A, J=8Hz), 7.0-7.2(lH, 7.3-7.35(2H, m) (a) W .3 0 (CDCl l) 2.663, 6.35(11, d, J=8Hz), 6.62 73 130.5-131.0 ad, J=3Hz, 1Hz, 6.71(1, d, J=31z), 6.76 s- UH d, J=8~z) 7.52$lHI d, J=1Ei (G(DC1 2.63(3, 6.41111, d, J=81z), 74 130,5-31.0 6.77, d, J=8z), 7.15(H, m)n 7)3-7.5 I ii(2H, m) S48 The following ,rmulation Examples illustrate the preparation of the agricultural-horticultural fungicide or fungicidal composition of this invention. The active ingredient compounds are shown by the compound numbers given in Table 1. All parts are by wwight.

FORMULATION EXAMPLE 1 Dust:- Three parts of compound No. 5, 20 parts of diatomaceous earth, 30 parts of terra alba, and 47 parts of talc were pulverized and mixed uniformly to obtain 100 parts of a dust.

FORMULATION EXAMPLE 2 Wettable powder:- Thirty parts of compound No. 19, 47 parts of diatomaceous earth, 20 parts of terra alba, 1 part of sodium ligninsulfonate and 2 parts of sodium alkylbenzenesulfonate were unfiromly pulverized and mixed to give 100 parts of a wettable powder.

FORMULATION EXAMPLE 3 Emulsifiable concentrate:- Twenty parts of compound No. 6, 10 parts of cyclohexane, 50 parts of xylene and 20 parts of Sorpol (a trademark for a surface-active agent produced by Toho Chemical Co.# Ltd.) were uniformly mixed to form 100 parts of an emulsifiable concentrate.

FORMULATION EXAMPLE 4 Granules:- One part of compound No. 2, 78 parts of bentonite, 20 parts of talc and 1 part or szdium ligno- DV, 30 sulfonate were mixed, and a moderate amount of water was added, and the mixture was kneaded. The kneaded mixture ,was granulated by a customary method in an extrusiono granulation machine and dried to give 100 parts of granules.

FORMULATION EXAMPLE Granules:- I I L i 49 Five parts of compound No. 11, 1 part of polyethylene glycol nonyl phenyl ether, 3 parts of polyvinyl alcohol and 91 parts of clay were uniformly mixed. Water was added, and the mixture was granulated and dried to give 100 parts of granules.

FORMULATION EXAMPLE 6 Dust:- Two parts of compound No. 20, 40 parts of calcium carbonate and 58 parts of clay were uniforily mixed to give 100 parts of a dust.

FORMULATION EXAMPLE 7 Wettable powder:- Fifty parts of compound No. 37, 40 parts of talc, 5 parts of sodium laurylphosphate and 5 parts of sodium alkylnaphthalenesulfonate were mixed to give 100 parts of a wettable powder.

FORMULATION EXAMPLE 8 Wettable powder:- Fifty parts of compound No. 4, 10 parts of sodium lignosulfonate, 5 parts of sodium alkylnaphthalenesulfonate, 10 parts of white carbon and 25 parts of S' diatomaceous earth were mixed and pulverized to give 100 parts of a wettable powder.

FORMULATION EXAMPLE 9 Flowable agent:- Forty parts of compound No. 10, 3 parts of carboxymethyl cellulose, 2 parts of sodium lignosulfonate, 1 part of dioctyl sulfosuccinate sodium salt Sand 54 parts of water were wet-pulverized by a sand grinder to give 100 parts of a flowable agent.

FORMULATION EXAMPLE Dust:- 0 TWo parts of compound No. 2, 2 parts of metalaxyl, 20 parts of diatomaceous earth, 30 parts of 35 tetra alba and 45 parts of talc were mixed and pulverized a to give 100 parts of a dust.

i 1 *1 50 FORMULATION EXAMPLE 11 Wettable powder:- Fifteen parts of compounds No. 4, 15 parts of oxadixyl, 47 parts of diatomaceous earth, 20 parts of terra alba, 1 part of sodium lignosulfonate and 2 parts of sodium alkylbenzenesulfonate were uniformly pulverized and mixed to give 100 parts of a wettable powder.

FORMULATION EXAMPLE 12 Wettable powder:- Ten parts of compound No. 6, 20 parts of metalaxyl, 55 parts of talc, 3 parts of sodium laurylphosphate and 2 parts of sodium alkylnaphthalenesulfonate were mixed to give 100 parts of a wettable powder.

FORMULATION EXAMPLE 13 Wettable powder:- Five parts of compound No. 2, 15 parts of ofurace, 65 parts of diatomaceous earth, 10 parts of white carbon, 3 parts of sodium laurylphosphate and 2 parts of sodium alkylnaphthalenesulfonate were mixed to give 100 parts of a wettable powder.

FORMULATION EXAMPLE 14 Wettable powder:- Twenty parts of compound No. 2, 30 parts of benalaxyl, 35 part of talc, 10 parts of white carbon, 3 parts of sodium laueylphosphate and 2 parts of alkyl- S! naphthalenesulfonate were mixed to give 100 parts of a wettable powder.

FORMULATION EXAMPLE Emulsifiable concentrate:- S 30 Seven parts of compound No. 6, 10 parts of metalaxyl, 50 parts of phenoxyethanol, 28 parts of xylene, 3 parts of polyoxyelthylene styryl phenyl ether and 2 parts of sodium alkylnaphthalenesulfonate were mixed to give 100 parts of an emulsifiable concentrate.

35 FORMULATION EXAMPLE 16 Granules:- 1 i L It 51 Three parts of compound No. 17, 10 parts of metalaxyl, 84 parts of clay, 1 part of polyethylene glycol nonylphenyl ether and 2 parts of polyvinyl alcohol were uniformly mixed and kneaded with the addition of a moderate amount of water. The kneaded mixture was granulated by a conventional method using an extrusion-granulator, and dried to give 100 parts of granules.

FORMULATION EXAMPLE 17 Wettable powder:- Five parts of compound No. 4, 45 parts of mancozeb, 27 parts of diatomaceous earth, 20 parts of terra alba, 1 part of sodium lignosulfonate and 2 parts of sodium alkylbenzenesulfonate were pulverized and mixed uniformly to give 100 parts of a wettable powder.

FORMULATION EXAMPLE 18 Wettable powder;- Ten parts of compound No. 18, 50 parts of mancozeb, 35 parts of talc, 3 parts of sodium laurylphosphate and 2 parts of sodium alkylnaphthalenesulfonate o. were uniformly pulverized and mixed to give 100 parts of a wettable powder.

FORMULATION EXAMPLE 19 Wettable powder:- Five parts of compound No. 2, 50 parts of captan, 40 parts of talc, 3 parts of sodium laurylphosphate and 2 parts of sodium alkylnaphthalenesulfonate were uniformly pulverized and mixed to give 100 parts of a wettable powder.

FORMULARION EXAMPLE Wettable powder:- Ten parts of compound No. 2, 50 parts of captafol, 35 parts of talc, 3 parts of sodium laurylphosphate and 2 parts of sodium alkylnaphthalenesulfonate were pulverized and mixed uniformly to give 100 parts of a wettable powder.

K- K- -52 FORMULATION EXAMPLE 21 Wettable powder:- Five parts of compound No. 6, 50 parts of folpet, 40 parts of talc, 3 parts of sodium laurylphosphate and 2 parts of sodium alkylnapthalenesulfonate were uniformly pulverized and mixed to give a wettable powder.

FORMULATION EXAMPLE 22 Wettable powder:- Five parts of compound No, 4, 50 parts of basic copper chloride, 40 parts of talcf 3 parts of sodium laurylphosphate and 2 parts of sodium alkylnaphthalenesulfonate were uniformly pulverized and mixed to give 100 parts of a wettable powder.

FORMULATION EXAMPLE 23 Wettable powder:- Seven parts of compound No. 4, 50 parts of basic copper sulfate, 38 parts of talc, 3 parts of sodium laurylphosphate and 2 parts of sodium alkylnaphthalenesulfonate were uniformly pulverized and mixed to give 100 parts of a wettable powder.

FORMULATION EXAMPLE 24 Wettable powder:- Five parts of compound No. 6, 50 parts of TPN, 40 parts of talc, 3 parts of sodium laurylphoaphate and 2 parts of sodium alkylnaphthalenesulfonate were uniformly pulverized and mixed to give 100 parts of a wettable powder.

FORMULATION EXAMPLE Wettable powdert- Seven parts of compound No. 2, 50 parts of zineb, 3 parts of sodium lignosulfonate, 3 parts of sodium alkylnaphthalenesulfonate, 7 parts of white carbon and 30 parts of diatomaceous earth were uniformly pulo 35 verizd and mixed to give 100 parts of a wettable powder.

I i 53 FORMULATION EXAMPLE 26 Wettable powder;- Three parts of compound No. 2, 50 parts of mancozeb, 3 parts of sodium lignosulfonate, 3 parts of sodium alkylnaphthalenesulfonate, 5 parts of white carbon, 16 parts of terra alba and 20 parts of diatomaceous earth were uniformly pulverized and mixed to give 100 parts of a wettable powder.

FORMULATION EXAMPLE 27 Five parts of compound No. 10, 50 parts of dichlofulanid, 40 parts of talc, 3 parts of sodium laurylphosphate and 2 parts of sodium alkylnaphthalenesulfonate were uniformly pulverized and mixed to give 100 parts of a wettable powder.

FORMULATION EXAMPLE 28 Granules:- One part of compound No. 2, 2 parts of polycarbamate, 85 parts of clay, 9 parts of diatomaceous earth, 1 part of polyethylene glycol nonyl-phenyl ether and 2 parts of polyvinyl alcohol were uniformly mixed, and further with the addition of a moderate amount of water, kneaded. The kneaded mixture was granulated by a conventional method in an extrusion-g anulator and dried to give 100 parts of granules.

FORMULATION EXAMPLE 29 Dust:- Two parts of compound No. 4, 20 parts of polycarbamate, 10 parts of diatomaceous earth, 20 parts of _I terra alba and 48 parts of talc were uniformly pulverized and mixed to give 100 parts of a dust.

The following Test Examples illustrate the efficacy of the compounds of this invention as the agricultural-horticultural fungicide and the agriculturalhorticultural fungicidal composition. The compounds used 35 in these test examples are indicated by the numbers shown S".J I in Table 1 or bhe symbols in Table 2.

O S -54 Table 2 A: Complex of manganese and zinc ethylenebis- (diethiocaL'3amates) (rancozeb] zinc ethylenebis(dithiocarbamate) [zineb] C: N-1 12~ 1,2 '-tetracloroethylthio-4-cyclohexene-l,2-dicarboximide [captafol) D: basic copper chloride E: tet rachlo roisophthalonit rile [TPNJ F: 3-chlo 2-pyr idyl) -2 ,6-d initro-4-trif luoromethylaniline fcichlofulanide] G: N-(2,,6-dimethylplienyl)-N-(2-methoxyacetyl3alanine methyl ester [metal.~xyl] H: N-(2,6-dimethylphenyl)-N-(2-furoyl)alariine methyl ester [furalaxyl] I: N-(2,6-diniethylphenyl)-N- ,phenylacetyl)alanine methyl ester (benalaxyll J: 2-chloro-N--(2,G-dimethylphenyl)-N-(tetrL,hydro-2-oxo.-3-furanyl)acetamide (ofuracel K; 2-methoxy-N-(2,6-dinethylphenyl).-N-(2oxo-1 ,3-o,\,aolidin-3-yl) acetamide (oxadixyl] Li: 3-chloro-N- (oxoperhiydro-3-furyl) -cyclopropanecarboxyanilide [cyprofurami M: N-(alpha-cyanofurfuryi.)-2,6-dichloropyiridine-4-carboxyllic acid amide N: N- (alpha-cy~inofucrfuryl) fur'Ane-2-carboxylic acid amide Note Compounds M and N are 6,escribed ii, the abovecited British Laid-Open Patent Application BP-2Q9523"i.

Compounds G to L are comm~ercial agricultural chomicals for controlling potato late blight a.iid cu~cumber dlowny, mildew.

TEST EX(AMPLE I Test for controlling potato late blight (preventive ef fect)- 55 A chemical (obtained by :,eparing a wettable powder of each test compound in accordance with the method of Formulation Example 8 and diluting it with water to a predetermined concentration) was applied to potato (variety: "danshaku"; plant height about 25 cm) grown in pots in a greenhouse at a rate of 50 ml per three pots by using a spray gun (1.0 kg/cm2), and then dried in the air. A zoospore suspension of Phytophthora infestans cultured for 7 days on a potato slice was sprayed and inoculated on the potato plant. The test plant was maintained at a temperature of 17 to 19 0 C and a humidity of rTore than 95 for 6 days, and then the degree of form~ation of lesions was examined.

The proportion of the area of lesions was observed and evaluated in each of the leaves, and the index of degree of the disease (disease index) was determined. In each of the test areas, the lesion index was calculated in accordance with the following equation.

4n4 3n 3 2n 2 In i On 0 Lesion index,- 3 2 0

N

The standards of evaluation are as follows:- Dit use Index Proportion of the area of lesion 0 1 25 2 6 2 3 26 4 51 or more no: the number of leaves with a disease index of 0 Sn: the number of leaves with a disease index of 1 n 2 the number of leaves with a disease index of 2 n3: the number of leaves with a disease index of 3 4: the number of leaves with a disease index of 4 N=n0 n1 n2 n3 n 4 I

C

56 TEST EXAMPLE 2 Test for controlling potato late blight (curative effect):- A zoospore suspension was prepared from Phytophthora infestans cultured for 7 days on a potato slice was inoculated by spraying on potato (variety: "danshaku"; plant height about 25 cm) grown in pots in a greenhouse.

The pots were maintained at 17 to 19 °C for 20 hours, and then a chemical having a predetermined concentration (obtained by preparing a wettable powder of each test compound in accordance with the method of Formulation Example 8 and diluting it with water to the predetermined cncentration) was sprayed onto the potato plants at a rate of 50 ml per three pots by using a spray gun kq/cm2), and then dried in the air. The pots were maintained at a temperature of 17 to 19 °C and a humidity of more than 95 for 6 days, and then the degree of formation of lesions was examined. The standards of evaluation and the method of indicating the lesion index were as shown in Test Example 1.

TEST EXAMPLE 3 I Test for controlling cucumber downy mildew (preventive effect):- A chemical in a predetermined concentration oo; 25 (obtained by preparing a wettable powder of each test compound in accordance with the method of Formulation Example 8 and diluting it with water to the predetermined concentration) was sprayed on cucumber (variety: "Sagami AO hanjiro; in the stage where two main leaves were developed) grown in pots in a greenhouse at a rate of 30 ml per three pots using a spray gun (1.0 kg/cm2), and dried in the air. Pseudoperonospora cubenis were taken from the Slesion of cucumber leaves infected with downy mildew and a spore suspension was prepared by using deionized water, and inoculated by spraying on the cucumber. Immediately then, the inoculated pots were maintained at a tempera-

I]

57 ture of 18 to 20 °C and a humidity of more than 95 for 24 hours, and then transferred to a greenhouse (at 18 to 27 oC). Seven days later, the degree of formation of lesions was examined.

The standards of evaluation and the method of indicating the lesion index were as shown in Test Example.

1.

TEST EXAMPLE 4 Test for controlling cucumber downy mildew (curative effect):- As in Test Example 3, a spore suspension of Pseudoperonospora cubenis was prepared, and inoculated by spraying on the same cucumber as used in Test Example 3. Immediately then, the inoculated pots were maintained at a temperature of 18 to 20 °C and a humidity of more than 95 for 24 hours. A chemical in a predetermined concentration (obtained by preparing a wettable powder of each test compound in accordance with the method of Formulation Example 8 and diluting it with water to the predetermined concentration) was sprayed on the cucumber at a rate of 30 ml per three pots using a spray gun Skg/cm 2 and dried in the at he pots were then transferred to a greenhouse (at 18 to 27 and 7 days later, the degree of formation of lesions was examined.

The standards of evaluation and the method of indicating the lesion index were as shown in Test Example 1.

TEST EXAMPLE Test for controlling tomato late blight (soil drench):- A chemical in a predetermined concentration (obtained by preparing a wettable powder of each test compound in accordance with the method of Formulation Example 8 and diluting it with water to the predetermined concentration) was drenched into th soil near the roots of tomato (variety: "sekaiichi"; height 20 cm) grown in L

I

-58pots (7.5 cm in diameter) in a greenhouse by mans of a pipette at a rate of 2 ml per pot. The pots were then maintained in the greenhouse for 5 days. A zoospore suspension was prepared from Phytophthora infestans cultured for 7 days on a potato slice. The suspension was then inoculated by spraying on the chamical-treated tomato plants. The test plants were maintained at a temperature of 17 to 19 oC and a humidity of more than and the degree of formation of lesions was examined.

In the above Test Examples, the concentration of the active ingredients was adjusted to 100 ppm in the case of spraying, and to 15 g/acre in the case of soil drench.

The results of the above Test Examples are shown in Table 3.

TEST EXAMPLE 6 Test for controlling cucumber downy mildew (curative effect a'nd resid~;al effect):- Pseudoperonospora cubenis was taken from the lesions on the leaves of cucumber (variety: "Sagami hanjiro"; in the stage where three main leaves were developed) grown in pots in a greenhouse, and using deionzied water, a spore suspension of the fungus was prepared. The spore suspension was inoculated by spraying on the acuumber plants. The inoculated pots were maintained for 24 hours in the greenhouse, and a S.o chemical in a predetermined concentration (obtained by preparing a wettable powder of each test compound in accordance with the method of Formulation Example 18 or 19 and 'diluting it to the predetermined concentration) at rate of 50 ml per three pots by using a spray gun kg/cm and dried in the air. Then, the pots were transferred to a greenhouse (18 to 27 and 10 and 1 59 18 days later, the degree of formation of lesions was examined. The results are shown in Table 4.

TEST EXAMPLE 7 Test for controlling tomato late blight (curative effect and residual effect):- A zoospore suspension was prepared from Phytophthora infestans cultured on a potato slice for 7 days, and inoculated by spraying on tomato (variety: "sekaiichi"; plant height 20 cm) grown in pots in a greenhouse. The inoculated pots were maintained for 24 hours in a humid chamber kept at 16 0 C, and a chemical in a predetermined concentration (obtained by preparing wettable powder of each test compound in accordance with Formulation Example 18 or 19, and diluting it with water to the predetermined concentration) was sprayed onto the plants at a rate of ml per three pots by using a spray gun (1.0 kg/cm2), and dried in the air. The pots were transferred to a greenhouse (10 to 20 oC), and 10 days and 11 days later, the degree of formation of lesions was examined. The results are shown in Table The standards of evaluation and the method of indicating the lesion inJex were as shown in Test Example 1.

TEST EXAMPLE 8 Test for controlling cucumber downy mildew (effect on a resistant strain to acylalanine chemicals):- A chemical in a predetermined concentration (obtained by preparing a wettable powder of each test compound in accordance witi ormulation Example 11 or 12 and diluting it with water to the predetermined concentration) was sprayed onto cucumber (variety: "Sagami 35 hanjiro"; the stage where three main leaves were de- 9 It~llr(

B

B1 D D I p U 01 1.- 60 veloped) grown in pots in a greenhouse at a rate of 50 ml per three pots by using a spray gun (1.0 kg/cm2), and dried in the air. Each of Pseudoperonospora cubenis resistant and sensitive strain to acylalanine fungicide was taken from the lesions of cucumber leaves infected with downy mildew. They were mixed and a spore suspension was prepared from the mixture. The spore suspension was then inoculated on the treated cucumber leaves by spraying. The inoculated pots were maintained in a humid I0 chanber at 20 °C for 24 hours, and then transferred to a greenhouse (18 to 27 0 Ten days and 18 days later, the degree of formation of lesions was examined. The lesion index was determined as in Test Example 1. The results are shown in Table 6.

TEXT EXAMPLE 9 Test for controlling tomato early blight:- A chemical in a predetermined concentration (obtained by preparing a wettable powder of each test compound in accordance with Formulation Example 18 and diluting it with water to the predetermined concentration) was sprayed on tomato (variety: "sekaiichi"; plant height about 20 cm) grown in pots in a greenhouse at a rate of ml per three pots by using a spray gun (1.0 kg/cm 2 and dried in the air. A spore suspension of Alternaria solani cultured in a PSA medium, and inoculated on tamato in the pots by spraying. The pots were transferred to a o greenhouse (25 to 33 and 10 days later, the degree of formation of lesions was examined. The lesion index was determined as in Test Example 1, and the results are shown in Table 7.

The results given in Table 3 demonstrate that the compounds of this invention shows excellent control I effect against plant diseases induced by Oomycetes, such as potato late blight, tomato late blight and LK

VA

61 cucumber downy mildew, not only in spraying but also in soil drench, whereas control compounds M and N considered to be relatively similar to the compounds of this invention show little or no control effect on these plant diseases. Furthecmore, the compounds of this invention show a preventive effect at mich lower dosages than zinc ethylenebis(dithiocarbmate) and tetrachloroisophthalonitrile commeiLially available and widely used against these plant diseases, and have a curative effect which these two commercial chemicals do not have. Accordingly, the compounds of this invention can exhibit a good control effect even when they are applied after crops have been infected with these diseases. Thus, this can greatly change the disease conrol system for agricultural and horticultural crops, and will evidently contribute greatly to labor saving on the part of the grower. Since the compounds of this invention have a good control erfect when applied by soil drench, and enable that part of a plant which the chemical is not expected to reach by spraying alone to be protected from diseases.

The results given in Tables 4 and 5 show that y the agricultural-horticultural fungicidal composition in accordance with this invention shows a very superior S control effect at lower dosages than in the case of using the dithiocarbamates, N-haloalkylthioimides, inorganic i copper fungicides, TPN, thiazole derivatives and isothiazole derivatives as the active ingredients.

Evidently, the syner .istic effect owing to mixing is noted and tht residual effect is very much strengthened.

The results given in Table 7 show that the agricultural-horticultural fungicidal composition has an excellent control effect on a broad range of plant diseases induced by plant pathogenic fungi, such as Alternaria *0 solani, Pseudoperonospora cubenis -*ld Colletotichum lagenarium which are taxonomically remote from each

I

62 other. This means that in the cultivation of crops the application of the agricultural-horticultural fungicidal composition can control a plurality of simultaneously occurring plant diseases which are difficu't to control simultaneously by conventional fungicidal compounds.

As shown in Table 6, the agricultural-horticultural fungicidal composition has sn excellent control effect against a wide range of plant diseases induced by Oomycetes whose resistance to fungicidal chemicals is a serious problem. Specifically, the agricultural-horticultural fungicidal composition of this invention shows a much better control effect at lower dosages than in the case of singly using acylalanine fungicides (such as metalaxyly furalaxyl, benalaxyl, o>adixyl, ofurace and cyprofuram), thiazoles derivaives and isothiazole derivatives, the active ingredients of this composition.

Evidently, a synergistic effect is exhibited as a result of mixing.

L. i 2 63 Table 3 Test on diseases Of potato, cucumber and tomato Test Lesion indpzx Com-, pound Potato Cucumber Tomat No. late blight downy mildew late blight Pre- Cur- Pre- Cur- Soil ventive ative ventive a%-ive drain 2 0 0 0 0 0 3 0 -0 0 0 4 0 0 00 6 0 0 00 6 n-00 0 7 0 0 0 00 8 0.3 -0.2 0O 0.2 9 0 00 0 0 0 0 0 0 11 0 0 0 0 0 12 0 0 0 0 0 13 0 0 0 0 14 0 0 0 0 0 is0 0 0 0 0 16 0 0 0 0 17 0 000 0 18 0 0 0 0 19 0 0 0 0 20 0 000 0 to bo continued- 4 44 o Q

V

64 Table 3 (continued) Test Lesion index pound Potato Cucumber Tomato N.late blight downy mildew late blight Pre- Cur- Pre- Cur- soil ventive ative ventive ative drain 21 0 0 0 0 22 0 0 0 0 0 0 0 0 0 26 0 0 0 0 32o 0 0 0 0 o3 0 0 0 0 3400 0 0 0 3500000 360000 38 0 0 0 0 39 0 0 0 0 0 0 0 0 41 0 0 0 0 42 0.5 0.6 0.3 0.3 43 1.2 1.2 1.0 44 0 0 0 0 0 0 0 0 46 0 0 0 0 47 0 0 0 0 48 0o 0 0 0 5__I010 0 0 -to be continued-

-N

C, I L 65 Table 3 (continued) Test Lesion index Com-- pound Potato Cucumber ITomate No. late blight downy mildew jlaite blight Pre- Cur- Pre- Cur- Soil ventive ative ventive ative drain 51 0 0 0 0 0 52 00 0 0 0 53 00 0 0 0 54 0 0 0 0 0 0 0.5 56 0.3 58 0 0 0 59 0 0 0 0 0 0 0 0 0 61 0 0 0 0 62 0 0.4 0 0 -0 0 71 0 0.2 73 0 0.2 M 2.0 2.4 2.1 2.4 3.2 N 2.0 2.5 1.9 2.3 B 2.3 3.8 2.0 3.4 3.8 E 2.4 3.6 2.5 3.7 3.7 Nontreated 3.7 3.7 3.7 3.8 66 Tab le 4 Test on cucumber downy mildew Test Concentration Lesion index co~mpound of the active~____ No., ingredient (ppm) 10 days 18 days later later 2 300 0 0.7 0 3 100 0 J-.0 0 1.3 4 100 0 0.7 j O 100 0 0 1 6 100 0 1- 1 17 100 00.8 so 0 0.8 18 100 00.6 00.7 A 502.9 2.9 D 500 3.53.

.503.0 3.1 F500 2.7 2.8 2A100+1500 0 0 50+500 00 3+A 100+500 0 0 50+500 0 0 4+A 100+500 0 0 50+500 0 0 100+500 0 0 50+50 0 0 0 -to be continued- -p ££ft Lz~ Th 67 Table 4 (continued) Test Concentration Lesion index compound of the active No. ingredient (ppm) 10 days 18 days later later, 2+C 100+500 0 0 50+500 0 0 6+C 100+500 I 0 0 50+500 0 0 1'7+C 100+500 0 0 50+500 0 0 18+C 100+500 0 0 50+500 0 0 3+D 100+500 0 0 50+500 0 100+500 0 0 50+500 0 0'.2 18+D 100+500 0 0.1 50+500 0 2+E 100+500 0 0 50+500 0 0 6+E 100+500 0 0 50+500 0 0 17+E 100+500 0 0 50+500 0 0 18+E 100+500 0 0 50+500 0 0 2+F 100+500 0 0 50+500 0 0 W+ 100+500 0 0 50+500 0 0 10+0 0 50+500 0 0 teted 3. 1 .7 0 11 0 0 4 4 04 04~ 0 4 p 0 04 ~0 04 -68 Table Test on tomato late blight Test Concentration Lesion index compound of the active No. ingredient (ppm) 10 days 18 days later later 2 100 0 0.8 0 1.2 6 100 0 1.1 0 1.4 12 100 0 0.7 0 13 100 0 0.6 Sk0 0 0.9 50100 01.

0 54 1 100 0 A 50 0 1.8 A500 3.3 C 500 3.5 3.6 D 500 3.5 E 500 F 500 3.0 2+A 100+500 0 0 50+500 0 0 6+A 100+500 0 0 50+500 0 0 13+A 100+500 0 0 50+500 0 0 54+A 100+500 0 0 I 5 0+5~00 0 0.4 2+C 1 100+500 1 0 0 50+500 0 0 44 6 6 66 64 14 II 04 0 06 -to be continued p

I

69 Table 5 (continued) Test Concentration Lesion index compound jof the active No. ingredient (ppm) 10 days 18 days later later' 6+C 100+500 0 0 0,15 00 0 0 100+500 0 0 50+500 0 0 12+D 10,0+500 0 0IJ 504,500 0 0A, 13+D 100+500 0 0 50+500 0 0 54+D 100+500 0 0.4 50+500 0.1 1~.7 2+E 100+500 0 0 50+500 0 0.4 6+E 100+500 0 0 50+500 0 0 100+500 0 0 50+500 0 0, 6+F 100+500 0 0 50+500 0 0 50F100+500 0 0 50+500 0 0 54+F 100+500 0 0 50+500 0 0 Non- 3.38 treated-3.38 00 C; C 4 CC CC .S I a a' a I I a' a a' I Ia a' a a' a' a'a'a'a a' a' 100 a' I CIlia' 4 a' a a' a' a' I a' 414

F

70 Table 6 Test on cucumber dowany meldew Test Concentration Lesion index compound of the active No. ingredient (ppm) 10 days I18 days later jlater 2 2Ci 0 0.6 100 0 1.1 4 200 0 100 0 200 0 0.9 100 0 6 200 0 100 0.5 G 200 2.4 100 2.4 H 200 2.2 2.8 100 2.5 3,15 1 200 1.7 100 1.6 2.2 J200 2.0 3.1 100 2.5 3.3 K 200 1. 1.8 100 1.9 L 200 1.3 100 1.3 2.8 2+G 50+50 0 0 50+100 0 0 4+G 50+50 0 0 50+100 0 0 50+50 0 0 50+100 0 0 6+G 50+50 0 0 50+10 0 0 0 -to be continued 0 4~4 P 0 45 44 <4 44 44 -71- Table 6 (continued) Test Concentration Lesion index compound of the active No. ingredient (ppm) 10 days 18 days later later, 2+H1 50+50 0 0 50+100 0 0 4+H1 50+50 0 0 50+100 0 0 5+11 50+50 0 0 50+100 0 0 6+H1 50+50 0 0.2 50+100 0 0.2 +150+50 0 0 50+100 0 0 4+1 50+50 0 0 50+100 0 0 5+1 50+50 0 0 50+100 0 0 6+1 50+50 0 0.3 50+100 0 0.1 2+J 50+50 0 0 50+100 0 0 4+J 50+50 0 0 50+100 0 0 50+50 0 0 50+100 0 0 6 50+50 0 0.3 50+100 0 0.1 2+K 50+50 0 0 50+100 0 0 4+K 50+50 0 0 50+100 0 0 5+K( 50+50 0 0 50+100 0 0 to be continued-

I

4 4~ 4 4 4 44 4 44 44 4 o ~4 4 4 4 4 4 4 4 0 p 0 4 0 72 Table 6 (continued) Test Concentration Lesion index compound of the active No. ingr~edient IrppM) 10 days 18 days later later' 6+K 50+50 0 0.3 50+100 0 0.2 2+L 50+50 0 0 50+100 0 0 4+L 50+50 0 0 50+100 0 0 50+50 0 0 50+100 0 0 6+L 50+50 0 0 50+100 0 0 Non-3. treated- 0 0.

4 4 14 1444 4 4144

I

444044 44 0 44444'

I

44 1 44 44 44 73 Table 7 Test on tobato early b1l':,ht Test Concentration Lesion compound ct the active index No. i Iredient (ppm) 2 i00 2.6 3 100 4 100 3.1 6 100 12 100 2.7 18 100 2.9 A. 500 0.8 E 500 0.7 F 500 2+A 100+~500 0 3+A 100+500 0 12+A 100+500 0 4+E 100+500 0 6+E 100+500 0 18+E 100+500 0 2+F 100+500 0 2 +F 100+500 0 12+F 109+500 0 Itreated 2 S 24. 0424 2 0

I

Claims

1. An amide derivative represented by the following general formula (I) 1 2 S ONHCH (I) Y R N wherein one of X and Y represents a sulfur atom and the other represents a carbon atom, Z represents a nitrile or thioamide group, each of R and R represents a hydrogen atom, a halogen atom, an alkyl group having 1 to 6 carbon atoms, a halomethyl group or a phenyl group, and R 3 represents an alkenyl group having 2 to 6 carbon atoms, a haloalkenyl group having 2 o 4 carbon atoms, or an unsubstituted or halo-substituted phenyl group.

2. The compound of claim 1 in which in general formula Z represents a nitrile group, each of R and R S represents a hydrogen atom or an alkyl group having 1 to 6 carbon atoms, and R represents a 2-methylpropen-l-yl group, o s

3. The compound of claim 1 in which in general formula Z represents a nitrile group, each of R and R represents a hydrogen atom or an alkyl group having 1 to 6 3 ca:bon atoms, and R represents a phenyl group.

4. The compound of claim 1 in which in general formula X represents a sulfur atom, Y represents a carbon atom, Z 1 2 represents a nitrile group, each of R and R represents an alkyl group having 1 to 6 carbon atoms, and R reresents a 2-methylpropen-l-yl group. The compound of claim 1 in which in general formula X represents a sulfur atom, Y represents a carbon atom, Z represiets a nitrile group, and each of R and R A represents an alkyl group having 1 to 6 carbon atoms, and R 3 represents a phenyl group.

6. An agricultural-horticultural fungicidal composition comprising a diluent or a carrier and/or an adjuvant, and as a first active ingredient at leait one amide derivative represented by the following general formula (I) 1 R 2 SX z -CONHCH 3 N wherein one of X and Y represents a sulfur atom and the other represents a carbon atom, Z represents a nitrile or thioamide group, each of R 1 and R represents a hydrogen atom, a halogen atom, an alkyl group having 1 to 6 carbon atoms, a halomethyl group or a phenyl group, and R represents an alkenyI "g group having 2 to 6 carbon atoms, a haloalkenyl group 2 having 2 to 4 carbon atoms, a furyl group, a thienyl group, an alkoxy group having 1 to 4 carbon atoms, an alkylthio group having 1 to 4 carbon atoms, an alkynyloxy group having 3 to 5 carbon atoms, an j alkynylthio group having 3 to 5 carbon atoms, a pyrazolyl group, or an unsubstituted or 0. halo-substituted phenyl group, and as a second active S. ingredient at least one of acylalanine fungicides having the action of controlling plant diseases caused by Oomycetes, dithiocarbamate fungicides, N-haloalkylthioimide fungicides, inorganic copper fungicides, tetrachloroisophthalonitrile, dichlofluanide and fluazinam.

7. The composition of claim 6 in which the second active ingredient is at least one acylalanine fungicide having the action of controlling plant diseases caused by Oomycetes.

8. The composition of claim 6 in which the second active A$?ZGR ingredient is at least one of dithiocarbamate fungicides, -76- N-haloalkylthioimide fungicides, inorganic copper fungicides, tetrachloroisophthalonitrile, dichlofulanide and fluazinam.

9. The composition of '.laim 6 in which the second active ingredient is a dithiocarbamate fungicide. The composition of claim 6 in which the second active ingredient is an N-haloalkylthioimide fungicide. The composition of claim 6 in which the second active ingredient is an inorganic copper fungicide.

12. The composition of claim 6 in which the first active ingredient is tetrachloroisophthalonitrile. a, 1I. The composition of claim 6 in which the second active ingredient is dichlofluanide. 040 14, The composition of claim 6 in which the second active o 2*0 ingredient is fluazinam.

15. An amide according to any one of claims 1 to substantially as herein described with reference to any one of the Examples.

16. A composition according to any one of claims 6 to 14 wherein said compound of formula I is as defined according to any one of the Examples. DATED: 12 May 1992 PHILLIPS ORMONDE FITZPATRICK Attorneys for: MITSUI TOATSU CHEMICALS, INC. 0264S Sl, 11I